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In the ventral horn of the sacral spinal cord of the cat, opioid terminals are preferentially localized in Onuf's nucleus, an area containing motor neurons that innervate the striated muscle of the external urethral sphincter. The... more
In the ventral horn of the sacral spinal cord of the cat, opioid terminals are preferentially localized in Onuf's nucleus, an area containing motor neurons that innervate the striated muscle of the external urethral sphincter. The present study was undertaken to 1) compare the effects of selective opioid agonists on sphincter reflex pathways with the effects of these drugs on hindlimb reflexes and urinary bladder reflexes and 2) determine if the physiological inhibition of sphincter reflexes, which accompany bladder contractions, is mediated by endogenous opioids. The effects of intrathecal (i.t.) and i.v. drug administration on bladder activity, sphincter reflexes and reflexes to the hindlimb musculature were monitored in chloralose-anesthetized cats. Ethylketocyclazocine (0.05-500 micrograms i.t.) produced a dose-dependent, naloxone-sensitive, inhibition of sphincter reflexes to less than 10% of control amplitude while having no consistent effects on hindlimb reflexes or bladder activity. D-Ser2-leu5-enkephalin-thr6 (DSLET; 0.1-2.0 micrograms i.t.) abolished rhythmic bladder activity, while having no effects on sphincter or hindlimb reflexes. Larger doses of DSLET (5.0-10 micrograms i.t.) produced a modest reduction of sphincter reflexes (to 60% of control amplitude), without affecting hindlimb reflexes. Naloxone (50 micrograms i.t.) reversed DSLETs marked inhibition of bladder activity, whereas large doses (greater than 250 micrograms i.t.) only partially antagonized DSLETs weak inhibition of sphincter reflexes. Morphine (5-500 micrograms i.t.) had no consistent effect on any of the measures.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Interests: Pharmacology, Cats, Urinary incontinence, Female, Animals, and 4 moreMorphine, Reflex, Naloxone, and Urinary Bladder
ABSTRACT
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... ions. Various aspects of the blockade by ACh or nicotine of transmission in untreated ganglia have been described (eg, Lundberg and Thesleff, 1953; Paton and Perry, 1953; Krivoy and Wills, 1956; Wurzel et al., 1962). The ...
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ABSTRACT
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Two main functions of lower urinary tract, storage and periodic elimination of urine, are regulated by a complex neural control system located in the brain and spinal cord which coordinates the activity of the reservoir (urinary bladder)... more
Two main functions of lower urinary tract, storage and periodic elimination of urine, are regulated by a complex neural control system located in the brain and spinal cord which coordinates the activity of the reservoir (urinary bladder) and the outlet (bladder neck, urethra and urethral sphincter). These organs are regulated by three sets of peripheral nerves: sacral parasympathetic (pelvic nerves), thoracolumber sympathetic nerves (hypogastric nerves) which innervate the bladder trigone and prostate, and sacral somatic nerves (pudendal nerves) which innervate external urethral sphincter (EUS). The relationship between the bladder and EUS is controlled by reflex pathways in the lumbosacral spinal cord that are activated by primary afferent input from the bladder or the urethra. This study was conducted to examine the reflexes that mediate bladder and sphincter coordination. We compared the properties of the pelvic nerve afferent to pudendal nerve reflex (pelvic-to-pudendal nerve re...
Isometric torques were generated about the knee joint by microstimulation of the cat lumbar L6 spinal cord. Stimulation via a single microelectrode in the ventral part of the L6 spinal cord produced large knee joint extension torques. The... more
Isometric torques were generated about the knee joint by microstimulation of the cat lumbar L6 spinal cord. Stimulation via a single microelectrode in the ventral part of the L6 spinal cord produced large knee joint extension torques. The extension torques were influenced by stimulus intensity, frequency and pulsewidth. Certain stimulation parameters (100 μA intensity, 40 Hz frequency and 0.20 ms
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The afferent innervation of the urinary bladder consists primarily of small myelinated (Adelta) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent... more
The afferent innervation of the urinary bladder consists primarily of small myelinated (Adelta) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions...
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1. [3H]Noradrenaline (NA) AND [14C]acetylcholine (ACh) released by electrical field stimulation were measured simultaneously in strips from the body of rat urinary bladder. 2. [3H]NA and [14C]ACh release was greater during continuous... more
1. [3H]Noradrenaline (NA) AND [14C]acetylcholine (ACh) released by electrical field stimulation were measured simultaneously in strips from the body of rat urinary bladder. 2. [3H]NA and [14C]ACh release was greater during continuous stimulation (CS; 10 Hz, 100 shocks) or in the presence of eserine than during intermittent train stimulation (IS; 10 Hz, 10 shocks every 5 s, 10 times). Atropine (1 microM) or pirenzepine (0.05-0.1 microM) blocked the CS- or eserine-facilitated release. 3. The protein kinase C (PKC) activator phorbol dibutyrate (PDB; 0.05 and 0.5 microM) increased the release of both [3H]NA and [14C]ACh in a concentration-dependent manner. Atropine blocked the PDB-induced facilitation of ACh release but not the facilitation of NA release. 4. The protein kinase A (PKA) activator 8-Br-cAMP did not affect ACh release but enhanced NA release. 5. The PKC inhibitor H-7 (50-100 microM) inhibited the CS- or eserine-facilitated release of both ACh and NA, but did not affect the ...
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Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents... more
Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats. Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method. In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after ...
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The effect of a non-symmetric waveform on nerve conduction block induced by high-frequency biphasic stimulation is investigated using a lumped circuit model of the unmyelinated axon based on Hodgkin-Huxley equations. The simulation... more
The effect of a non-symmetric waveform on nerve conduction block induced by high-frequency biphasic stimulation is investigated using a lumped circuit model of the unmyelinated axon based on Hodgkin-Huxley equations. The simulation results reveal that the block threshold monotonically increases with the stimulation frequency for the symmetric stimulation waveform. However, a non-monotonic relationship between block threshold and stimulation frequency is observed when the stimulation waveform is non-symmetric. Constant activation of potassium channels by the high-frequency stimulation results in the increase of block threshold with increasing frequency. The non-symmetric waveform with a positive pulse 0.4-0.8 μs longer than the negative pulse blocks axonal conduction by hyperpolarizing the membrane and causes a decrease in block threshold as the frequency increases above 12-16 kHz. On the other hand, the non-symmetric waveform with a negative pulse 0.4-0.8 μs longer than the positive...
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The purpose of this study was to determine the effect of tibial nerve stimulation (TNS) on the micturition reflex. Experiments were conducted in 24 rats under urethane anesthesia. A catheter was inserted into the bladder via the bladder... more
The purpose of this study was to determine the effect of tibial nerve stimulation (TNS) on the micturition reflex. Experiments were conducted in 24 rats under urethane anesthesia. A catheter was inserted into the bladder via the bladder dome for saline infusion. A cuff electrode was placed around right tibial nerve for stimulation. TNS (5 Hz, 0.2 msec pulse width) at 2-4 times the threshold (T) intensity for inducing a toe movement was applied either during slow (0.08 mL/min) infusion of the bladder or for 30 min with an empty bladder. TNS had no effect on the micturition reflex when it was applied during slow bladder infusion. However, the 30-min TNS applied with an empty bladder induced poststimulation inhibition and significantly (P < 0.05) increased the bladder capacity to about 140% of prestimulation level in a 50-min period following the termination of stimulation. The bladder compliance was also significantly (P < 0.05) increased after the 30-min TNS. These results sugg...
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OBJECTIVES: This study was undertaken to investigate whether chronic bladder outlet obstruction (BOO) in female rats influences the tonic parasympathetic excitatory or inhibitory reflex control of bladder activity. METHODS: Bladder... more
OBJECTIVES: This study was undertaken to investigate whether chronic bladder outlet obstruction (BOO) in female rats influences the tonic parasympathetic excitatory or inhibitory reflex control of bladder activity. METHODS: Bladder activity during isovolumetric cystometry (1.5-12 mL) was examined after transection of dorsal and ventral lumbosacral spinal roots (L4-S4) and administration of hexamethonium, a ganglionic blocking agent, in urethane anesthetized female rats with sympathectomy and BOO. RESULTS: Lumbosacral dorsal root transection abolished reflex bladder contractions, but did not influence intravesical baseline pressure. However, ventral root transection after dorsal root transection decreased baseline intravesical pressure (y: % change) at low bladder volumes (x) and increased pressure at high volumes. The calculated (y = 1.9x - 16.5) transition volume was 9 mL. Administration of hexamethonium (100 mg/kg, intraperitoneally) after dorsal and ventral root transection incre...
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The molecular mechanisms that regulate the organization and activity of the neuromuscular junction remain to be fully identified. Caveolae are invaginations of the plasma membrane. Caveolin-3 is the structural protein component of... more
The molecular mechanisms that regulate the organization and activity of the neuromuscular junction remain to be fully identified. Caveolae are invaginations of the plasma membrane. Caveolin-3 is the structural protein component of caveolae in muscle cells. We show that caveolin-3 is expressed at the neuromuscular junction, that it associates with the nicotinic acetylcholine receptor (nAChR), and that a lack of caveolin-3 inhibits clustering of the nAChR in myotubes. At the molecular level, we demonstrate that caveolin-3 is a novel muscle-specific kinase (MuSK) binding protein and that altered nAChR clustering in caveolin-3-lacking myotubes results from inhibition of agrin-induced phosphorylation/activation of MuSK and activation of Rac-1. Functional studies in caveolin-3 null mice show abnormal neuromuscular junction activity that is consistent with altered nAChR localization at the sarcolemma. Together, these data identify caveolin-3 as a critical component of the signaling machine...
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Changes in spontaneous activity of the urinary bladder during postnatal development were examined in muscle strips from the base and dome of bladders from 1- to 5-wk-old rats. Activity was analyzed using fast Fourier transformation (FFT),... more
Changes in spontaneous activity of the urinary bladder during postnatal development were examined in muscle strips from the base and dome of bladders from 1- to 5-wk-old rats. Activity was analyzed using fast Fourier transformation (FFT), nonlinear cross prediction, and the Shannon entropy test. Spontaneous activity was not detected in strips from 1- to 5-day-old rats but was observed in 50% of strips from 6- to 7-day-old rats and was prominent in strips from 2-wk-old animals. FFT analysis revealed one peak in activity, which was significantly faster in the bladder base (0.21 +/- 0.03 Hz) than in the dome (0.08 +/- 0.01 Hz). A second peak at approximately 0.5 Hz was detected at 3-5 wk of age. Atropine but not tetrodotoxin decreased the amplitude of spontaneous contractions, whereas carbachol, a muscarinic agonist, unmasked or stimulated spontaneous activity. These data suggest that slow rhythmic activity observed previously in neonatal whole bladders is generated by pacemaker cells ...
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The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle... more
The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle parts of the urethra increased, the response in the proximal urethra was almost negligible when the bladder response was subtracted from the urethral response or when the abdomen was opened. In contrast, the response in the middle urethra during sneezing was still observed after subtracting the bladder response or after opening the abdomen. These responses in the middle urethra during sneezing were significantly reduced approximately 80% by bilateral transection of the pudendal nerves and the nerves to the iliococcygeous and pubococcygeous muscles but not by transection of the visceral branches of the pelvic nerves and hypogastric nerves. The sneeze leak point pressure was also measured to investigate the role of active urethral closure mechanisms in...
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Nicotinic receptors in the brain modulate the release of many transmitters that are known to regulate voiding. This prompted us to examine the central nervous system effects of a neuronal nicotinic agonist, (+/-)-epibatidine, on voiding... more
Nicotinic receptors in the brain modulate the release of many transmitters that are known to regulate voiding. This prompted us to examine the central nervous system effects of a neuronal nicotinic agonist, (+/-)-epibatidine, on voiding function in awake and anesthetized rats. Intracerebroventricular injection of (+/-)-epibatidine (0.1 microg) significantly increased intercontraction interval (ICI) but did not change pressure threshold (PT) or maximal voiding pressure (MVP), whereas 1 microg of (+/-)-epibatidine increased PT and MVP (P < 0.05) and decreased ICI. A low intravenous dose of (+/-)-epibatidine (0.001-0.1 microg) had no effect; however, a large dose of (+/-)-epibatidine (1 microg) significantly decreased ICI and increased MVP (P < 0.05) but did not change PT (P > 0.05). The effects occurred within 5-10 min after injection and persisted for 1-2 h. Intracerebroventricular chlorisondamine (10 microg), a nicotinic receptor antagonist, blocked the effect of intracereb...
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Distension of the perfused guinea pig ureter at pressures from 20 to 700 cmH(2)O increased the amount of ATP released from the epithelium in a pressure-dependent manner. During basal perfusion (40 microl/min), the perfusate contained 10... more
Distension of the perfused guinea pig ureter at pressures from 20 to 700 cmH(2)O increased the amount of ATP released from the epithelium in a pressure-dependent manner. During basal perfusion (40 microl/min), the perfusate contained 10 pmol/ml ATP; this increased 10- to 50-fold at various distending pressures. ATP was released from epithelial cells during distension as mechanical removal of the urothelium blocked release. No lactate dehydrogenase was detected in the perfusate, and scanning electron microscopy confirmed an intact urothelium after distension. ATP was not released due to the activation of stretch-activated channels, as gadolinium (10 microM) failed to affect ATP release. Glibenclamide (10 microM), known to inhibit two members of the ATP-binding cassette (ABC) protein family, did not affect ATP release after distension; nor did verapamil (10 microM). In contrast, both monensin (100 microM) and brefeldin A (10 microM), which interfere with vesicular formation or traffic...
Research Interests: Physiology, Biomechanics, Scanning Electron Microscopy, Ion Channels, Animals, and 16 moreMale, Medical Physiology, Urinary Tract, Gadolinium, Rat, Urinary System, Oral Hypoglycemic Agents, Nociception, Exocytosis, S100 protein family, Pressure Gradient, Verapamil, Nociceptors, Adenosine Triphosphate, Calcium Channel Blockers, and Ureter
We used patch clamp recording techniques to determine if muscarinic signaling mechanisms are present in dissociated autonomic neurons obtained from the major pelvic ganglion, which provides the cholinergic innervation of the urinary... more
We used patch clamp recording techniques to determine if muscarinic signaling mechanisms are present in dissociated autonomic neurons obtained from the major pelvic ganglion, which provides the cholinergic innervation of the urinary bladder and other pelvic organs. The M1 specific agonist, McN-A-343 (2-30 microM) enhanced Ca2+ currents in approximately 37% of neurons (by 50-80%). This enhancement was reduced by atropine (5-10 microM) or a PKC inhibitor (bisindolylmaleimide, 50-200 nM). In responsive neurons Ca2+ currents were also enhanced by the phorbol ester, phorbol-12,13-dibutyrate (50-300 nM) and the dihydropyridine agonist Bay K 8644 (5 microM) and had kinetics of activation and inactivation as expected for L-type Ca2+ channels. We conclude that in a subpopulation of MPG neurons, M1-mediated activation of PKC phosphorylates and enhances L-type Ca2+ channel activities. This muscarinic facilitatory mechanism in MPG neurons may be the same as the M1-mediated facilitation of trans...
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1. 3H-Noradrenaline (NA) and 14C-acetylcholine (ACh) released by electrical field stimulation were measured simultaneously in strips from the body of rat urinary bladder. 2. omega-Conotoxin GVIA (omega-CgTX; 20-100 nM) suppressed the... more
1. 3H-Noradrenaline (NA) and 14C-acetylcholine (ACh) released by electrical field stimulation were measured simultaneously in strips from the body of rat urinary bladder. 2. omega-Conotoxin GVIA (omega-CgTX; 20-100 nM) suppressed the non-facilitated transmitter release evoked by intermittent stimulation (IS), whereas nifedipine (1 microM) did not affect release. 3. Continuous electrical stimulation (CS) facilitated NA and ACh release via an atropine-sensitive mechanism. omega-CgTX reduced the facilitated release of NA (44% depression) but did not affect ACh release. Nifedipine depressed ACh release (43%) but not NA release. Combined administration of nifedipine and omega-CgTX (20 nM) produced a greater suppression of NA and ACh release (86 and 91%, respectively). 4. Maximal muscarinic facilitation of NA (5-fold) and ACh (17-fold) release occurred following administration of eserine, an anticholinesterase agent. Release of both NA and ACh was depressed by nifedipine (70 and 83%, resp...
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Immunohistochemical and pharmacological studies were conducted to examine the origin and function of peptidergic nerves in the sacral autonomic system of the cat. Leucine-enkephalin (L-Enk) immunoreactivity was identified in nerve... more
Immunohistochemical and pharmacological studies were conducted to examine the origin and function of peptidergic nerves in the sacral autonomic system of the cat. Leucine-enkephalin (L-Enk) immunoreactivity was identified in nerve terminals in peripheral ganglia on the surface of the urinary bladder and in the parasympathetic nucleus in the sacral spinal cord. In colchicine-treated animals L-Enk was also detected in sacral preganglionic neurons (sPGN) identified by retrograde transport of a fluorescent dye. L-Enk terminals in bladder ganglia are believed to arise from sPGN since the terminals were eliminated by transection of the sacral ventral roots. Pharmacological studies indicated that exogenous as well as endogenously released enkephalins have an inhibitory action at both ganglionic and spinal sites in the sacral outflow to the urinary bladder. Peptides were also associated with afferents nerves in the sacral autonomic system. The distribution of substance P, VIP and cholecysto...
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Micturition in cats and rats with an intact neuraxis is dependent upon a spinobulbospinal reflex activated by A delta bladder afferents. This report describes changes in micturition reflexes 2 h to 14 weeks following spinal cord... more
Micturition in cats and rats with an intact neuraxis is dependent upon a spinobulbospinal reflex activated by A delta bladder afferents. This report describes changes in micturition reflexes 2 h to 14 weeks following spinal cord transection at the lower thoracic level. In acute spinal cats micturition reflexes were blocked, however, several weeks after transection, a long latency (180-200 ms) spinal reflex could be activated by C-fiber bladder afferents. This reflex was blocked by capsaicin in doses (20-30 mg/kg, s.c.) that did not affect micturition reflexes in intact cats. Micturition reflexes were unmasked in acute spinal and facilitated in chronic spinal cats by naloxone, an opioid antagonist. Spinal neurons and axons containing opioid peptides were more prominent below the level of transection in chronic spinal cats. VIP, a putative neurotransmitter in C-fiber bladder afferents, inhibited micturition reflexes when injected intrathecally (2-10 micrograms) in intact cats but faci...
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Nerve conduction block induced by high frequency biphasic electrical current was simulated using a lumped circuit model of the myelinated axon based on Frankenhaueuser-Huxley (FH) equations. Axons of different diameters (5-20... more
Nerve conduction block induced by high frequency biphasic electrical current was simulated using a lumped circuit model of the myelinated axon based on Frankenhaueuser-Huxley (FH) equations. Axons of different diameters (5-20 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#956;m) can be blocked completed when the stimulation frequency is above 10 kHz. At higher frequency a higher stimulation intensity is needed to block nerve conduction. Larger diameter axons have lower block threshold. The activation of potassium channels, rather than inactivation of sodium channels, is the possible mechanism underlying the nerve conduction block of the myelinated axon induced by high frequency biphasic pulse current. This simulation study, which provides more information about the axonal conduction block induced by high frequency biphasic pulse current, can guide future animal experiments as well as optimize stimulation waveforms for electrical nerve block in possible clinical applications.
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Cholinergic prejunctional modulatory receptors on parasympathetic nerves in the rat urinary bladder were studied by measuring 3H-acetylcholine (ACh) release in muscle strips from the bladder body. Electrical field stimulation markedly... more
Cholinergic prejunctional modulatory receptors on parasympathetic nerves in the rat urinary bladder were studied by measuring 3H-acetylcholine (ACh) release in muscle strips from the bladder body. Electrical field stimulation markedly increased 3H-ACh overflow in strips preloaded with 3H-choline. Oxotremorine (1 microM), an M2 receptor agonist and DMPP (10 microM) a nicotinic (N) receptor agonist decreased the release of ACh (50% and 55% respectively); whereas McN-A 343 (50 microM) an M1 receptor agonist increased the release (33%), indicating the presence of three types of modulatory receptors. The anticholinesterase agent, physostigmine in concentrations of 1, 5 and 25 microM and neostigmine (5 microM) increased ACh release (44-710%). However a low concentration of physostigmine (0.05 microM) decreased release. Pirenzepine, an M1 muscarinic antagonist or atropine blocked the increased ACh release in physostigmine-treated strips, but in normal strips pirenzepine did not change rele...
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Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca(2+) in 60-80% DRG neurons.... more
Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca(2+) in 60-80% DRG neurons. 1-Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA-NO2-sensitive neurons while capsaicin (TRPV1 agonist) or allyl-isothiocyanate (AITC, TRPA1 agonist) elicited responses in only 16% and 10%, respectively, of these neurons. A TRPV1 antagonist (diarylpiperazine, 5 μm) in combination with a TRPA1 antagonist (HC-030031, 30 μm) did not change the amplitude of the Ca(2+) transients or percentage of neurons responding to OA-NO2; however, a reducing agent DTT (50 mm) or La(3+) (50 μm) completely abolished OA-NO2 responses. OA-NO2 also induced a transient inward current associated with a membrane depolarization followed by a prolonged outward current and hyperpolarization in 80% of neurons. The reversal potentials of inward a...
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While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper... more
While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB.
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The existence of a pacemaker system in the urinary tract capable of orchestrating the movement of filtrated urine from the ureteral pelvis to the distal ureter and lower urinary tract seems intuitive. The coordinated activity necessary... more
The existence of a pacemaker system in the urinary tract capable of orchestrating the movement of filtrated urine from the ureteral pelvis to the distal ureter and lower urinary tract seems intuitive. The coordinated activity necessary for such movement or "peristalsis" would likely require an intricate network of cells with pacemaker-like activity, as is the case with the interstitial cells of Cajal (ICC) of the gut. We investigated whether these putative pacemaker cells of the urinary tract are antigenically similar to ICC of the gut by using immunofluorescence staining for c-kit, a cell-surface marker specific for ICC. Ureteral, urinary bladder, and urethral tissues were harvested from female mice of the WBB6F1 strain, and fixed sections were prepared and stained for c-kit. Cell networks composed of stellate-appearing, c-kit-positive, ICC-like cells were found in the lamina propria and at the interface of the inner longitudinal and outer circular muscle layers of the ur...
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The knee extensor and flexor EMG activity evoked by microstimulation of the cat L6 spinal cord were recorded while simultaneously monitoring the knee joint extension and flexion torques. Single fine-tipped (200 to 400 μm2 surface area)... more
The knee extensor and flexor EMG activity evoked by microstimulation of the cat L6 spinal cord were recorded while simultaneously monitoring the knee joint extension and flexion torques. Single fine-tipped (200 to 400 μm2 surface area) activated iridium microelectrode was implanted in the left side of the L6 spinal cord. Large extension torque was produced by microstimulation in the ventral
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We describe an in vitro method to measure bladder smooth muscle contractility, and its use for investigating physiological and pharmacological properties of the smooth muscle as well as changes induced by pathology. This method provides... more
We describe an in vitro method to measure bladder smooth muscle contractility, and its use for investigating physiological and pharmacological properties of the smooth muscle as well as changes induced by pathology. This method provides critical information for understanding bladder function while overcoming major methodological difficulties encountered in in vivo experiments, such as surgical and pharmacological manipulations that affect stability and survival of the preparations, the use of human tissue, and/or the use of expensive chemicals. It also provides a way to investigate the properties of each bladder component (i.e. smooth muscle, mucosa, nerves) in healthy and pathological conditions. The urinary bladder is removed from an anesthetized animal, placed in Krebs solution and cut into strips. Strips are placed into a chamber filled with warm Krebs solution. One end is attached to an isometric tension transducer to measure contraction force, the other end is attached to a fixed rod. Tissue is stimulated by directly adding compounds to the bath or by electric field stimulation electrodes that activate nerves, similar to triggering bladder contractions in vivo. We demonstrate the use of this method to evaluate spontaneous smooth muscle contractility during development and after an experimental spinal cord injury, the nature of neurotransmission (transmitters and receptors involved), factors involved in modulation of smooth muscle activity, the role of individual bladder components, and species and organ differences in response to pharmacological agents. Additionally, it could be used for investigating intracellular pathways involved in contraction and/or relaxation of the smooth muscle, drug structure-activity relationships and evaluation of transmitter release. The in vitro smooth muscle contractility method has been used extensively for over 50 years, and has provided data that significantly contributed to our understanding of bladder function as well as to pharmaceutical development of compounds currently used clinically for bladder management.
Research Interests: Medicine, In Vitro, Smooth muscle, Female, Animals, and 3 moreRats, Muscle contraction, and Urinary Bladder
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The lower urinary tract has two main functions, the storage and periodic expulsion of urine, which are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of... more
The lower urinary tract has two main functions, the storage and periodic expulsion of urine, which are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the pelvic floor). During urine storage the outlet is closed and the bladder is quiescent, thereby maintaining a low intravesical pressure over a wide range of bladder volumes. During micturition the outlet relaxes and the bladder contracts to promote the release of urine. This reciprocal relationship between bladder and outlet is generated by visceral reflex circuits, some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are presumably involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter functions. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. Studies in animals indicate that the recovery of bladder function after spinal cord injury is dependent in part on plasticity of bladder afferent pathways and the unmasking of reflexes triggered by capsaicin-sensitive C-fiber bladder afferent neurons. The plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons, and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs.
Research Interests: Cognitive Science, Spinal Cord Injury, Brain, Paraplegia, Humans, and 16 moreCerebral Cortex, Animals, Spinal Cord, Synaptic Transmission, Experimental Study, Urinary Tract, Vasoactive Intestinal Peptide, Reflex, Potassium Channels, Spinal Cord Injuries, Neural Control, Neurosciences, Interneurons, Glutamic Acid, Urinary Bladder, and sodium channels
During multimicroelectrode stimulation within the cat L6 spinal cord, the number of electrodes activated, their separation distance, and the stimulus interleave time all influenced isometric knee joint extension torque. The torque evoked... more
During multimicroelectrode stimulation within the cat L6 spinal cord, the number of electrodes activated, their separation distance, and the stimulus interleave time all influenced isometric knee joint extension torque. The torque evoked by stimulation with a three electrode combination could be enhanced or suppressed when compared with that evoked by single or paired electrode stimulation. A similar difference was noted