scholarly journals Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats

2017 ◽  
Vol 312 (3) ◽  
pp. F482-F488 ◽  
Author(s):  
Xuewen Jiang ◽  
Michelle Yu ◽  
Jamie Uy ◽  
Thomas W. Fuller ◽  
Cameron Jones ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Cannabinoid Receptor ◽  
Bladder Capacity ◽  
Intrathecal Administration ◽  
Saline Control ◽  
Cb1 Receptors ◽  
Pudendal Neuromodulation ◽  
Bladder Disorders

The role of cannabinoid type 1 (CB1) receptors in tibial and pudendal neuromodulation of bladder overactivity induced by intravesical infusion of 0.5% acetic acid (AA) was determined in α-chloralose anesthetized cats. AA irritation significantly ( P < 0.01) reduced bladder capacity to 36.6 ± 4.8% of saline control capacity. Tibial nerve stimulation (TNS) at two or four times threshold (2T or 4T) intensity for inducing toe movement inhibited bladder overactivity and significantly ( P < 0.01) increased bladder capacity to 69.2 ± 9.7 and 79.5 ± 7.2% of saline control, respectively. AM 251 (a CB1 receptor antagonist) administered intravenously at 0.03 or 0.1 mg/kg significantly ( P < 0.05) reduced the inhibition induced by 2T or 4T TNS, respectively, without changing the prestimulation bladder capacity. However, intrathecal administration of AM 251 (0.03 mg) to L7 spinal segment had no effect on TNS inhibition. Pudendal nerve stimulation (PNS) also inhibited bladder overactivity induced by AA irritation, but AM 251 at 0.01–1 mg/kg iv had no effect on PNS inhibition or the prestimulation bladder capacity. These results indicate that CB1 receptors play an important role in tibial but not pudendal neuromodulation of bladder overactivity and the site of action is not within the lumbar L7 spinal cord. Identification of neurotransmitters involved in TNS or PNS inhibition of bladder overactivity is important for understanding the mechanisms of action underlying clinical application of neuromodulation therapies for bladder disorders.

scholarly journals Involvement of 5-HT3 receptors in pudendal inhibition of bladder overactivity in cats

2013 ◽  
Vol 305 (5) ◽  
pp. F663-F671 ◽  
Author(s):  
Zeyad Schwen ◽  
Yosuke Matsuta ◽  
Bing Shen ◽  
Jicheng Wang ◽  
James R. Roppolo ◽  
...  
Keyword(s):  
High Intensity ◽  
Bladder Capacity ◽  
Saline Control ◽  
Low Intensity ◽  
Afferent Nerves ◽  
Normal Bladder ◽  
Pudendal Neuromodulation ◽  
Bladder Symptoms ◽  
Bladder Activity

In the present study, the role of 5-HT3 receptors in pudendal neuromodulation of bladder activity and its interaction with opioid receptors were investigated in anesthetized cats. The bladder was distended with either saline to induce normal bladder activity or with 0.25% acetic acid (AA) to induce bladder overactivity. Pudendal afferent nerves were activated by 5-Hz stimulation at multiples of the threshold (T) intensity for the induction of anal twitching. AA irritation significantly reduced bladder capacity to 16.5 ± 3.3% of saline control capacity, whereas pudendal nerve stimulation (PNS) at 1.5–2 and 3–4 T restored the capacity to 82.0 ± 12% ( P = 0.0001) and 98.6 ± 15% ( P < 0.0001), respectively. Cumulative doses (1–3 mg/kg iv) of ondansetron, a 5-HT3 receptor antagonist, eliminated low-intensity (1.5–2 T) PNS inhibition and reduced high-intensity (3–4 T) PNS inhibition of bladder overactivity. During saline distention, PNS at 1.5–2 and 3–4 T significantly increased bladder capacity to 173.2 ± 26.4% ( P = 0.036) and 193.2 ± 22.5% ( P = 0.008), respectively, of saline control capacity, but ondansetron (0.003–3 mg/kg iv) did not alter PNS inhibition. Ondansetron (0.1–3 mg/kg) also significantly ( P < 0.05) increased control bladder capacity (50–200%) during either AA irritation or saline distention. In both conditions, the effects of low- and high-intensity PNS were not significantly different. After ondansetron (3 mg/kg) treatment, naloxone (1 mg/kg iv) significantly ( P < 0.05) decreased control bladder capacity (40–70%) during either AA irritation or saline distention but failed to affect PNS inhibition. This study revealed that activation of 5-HT3 receptors has a role in PNS inhibition of bladder overactivity. It also indicated that 5-HT3 receptor antagonists might be useful for the treatment of overactive bladder symptoms.

scholarly journals Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats

2015 ◽  
Vol 308 (1) ◽  
pp. R42-R49 ◽  
Author(s):  
Marc J. Rogers ◽  
Zhiying Xiao ◽  
Bing Shen ◽  
Jicheng Wang ◽  
Zeyad Schwen ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Nerve Stimulation ◽  
Adrenergic Receptor ◽  
Bladder Capacity ◽  
Spinal Reflex ◽  
Saline Control ◽  
Tibial Nerve Stimulation ◽  
Bladder Activity ◽  
Propranolol Treatment

This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly ( P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly ( P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant ( P < 0.05). Propranolol treatment also significantly ( P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly ( P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β1/β2-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity.

PD70-07 ROLE OF CANNABINOID RECEPTOR TYPE 1 IN TIBIAL AND PUDENDAL NEUROMODULATION OF BLADDER OVERACTIVITY IN CATS

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Xuewen Jian ◽  
Michelle Yu ◽  
Jamie Uy ◽  
Thomas W. Fuller ◽  
Cameron Jones ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 1 ◽  
Pudendal Neuromodulation

scholarly journals Role of spinal GABAA receptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

2014 ◽  
Vol 306 (7) ◽  
pp. F781-F789 ◽  
Author(s):  
Zhiying Xiao ◽  
Jeremy Reese ◽  
Zeyad Schwen ◽  
Bing Shen ◽  
Jicheng Wang ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Bladder Capacity ◽  
Aminobutyric Acid ◽  
Saline Control ◽  
Receptor Subtype ◽  
High Dose ◽  
Multiple Threshold ◽  
Bladder Activity ◽  
Subtype A

Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly ( P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly ( P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly ( P < 0.05) reduced 2T PNS inhibition at low doses (0.01–0.1 mg/kg). During saline cystometry, PNS significantly ( P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03–0.3 mg/kg iv) also significantly ( P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.

scholarly journals Sympathetic afferents in the hypogastric nerve facilitate nociceptive bladder activity in cats

2019 ◽  
Vol 316 (4) ◽  
pp. F703-F711 ◽  
Author(s):  
Yan Zhang ◽  
Shun Li ◽  
Todd Yecies ◽  
Tara Morgan ◽  
Haotian Cai ◽  
...  
Keyword(s):  
Bladder Capacity ◽  
Saline Control ◽  
Pelvic Nerve ◽  
Analgesic Agent ◽  
Hypogastric Nerve ◽  
C Fibers ◽  
Pelvic Nerves ◽  
C Fiber ◽  
Bladder Activity

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.

scholarly journals Computer modeling of Cannabinoid receptor type 1

2018 ◽  
Vol 16 ◽  
pp. 02008
Author(s):  
Fatima Sapundzhi ◽  
Tatyana Dzimbova ◽  
Nevena Pencheva ◽  
Peter Milanov
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Scoring Function ◽  
Docking Studies ◽  
Cb1 Receptors ◽  
Important Class ◽  
Pain Sensation ◽  
Physiological Processes ◽  
Selective Ligands

Cannabinoid receptors are important class of receptors as they are involved in various physiological processes such as appetite, pain-sensation, mood, and memory. It is important to design receptor-selective ligands in order to treat a particular disorder. The aim of the present study is to model the structure of cannabinoid receptor CB1 and to perform docking between obtained models and known ligands. Two models of CBR1 were prepared with two different methods (Modeller of Chimera and MOE). They were used for docking with GOLD 5.2. It was established a high correlation between inhibitory constant Ki of CB1 cannabinoid ligands and the ChemScore scoring function of GOLD, which concerns both models. This suggests that the models of the CB1 receptors obtained could be used for docking studies and in further investigation and design of new potential, selective and active cannabinoids with the desired effects.

scholarly journals Role of Cannabinoid Receptor Type 1 Desensitization in Greater Tetrahydrocannabinol Impairment of Memory in Adolescent Rats

2010 ◽  
Vol 335 (2) ◽  
pp. 294-301 ◽  
Author(s):  
Nicole L. T. Moore ◽  
Ashley L. R. Greenleaf ◽  
Shawn K. Acheson ◽  
Wilkie A. Wilson ◽  
H. Scott Swartzwelder ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 1 ◽  
Adolescent Rats

scholarly journals Differential role of opioid receptors in tibial nerve inhibition of nociceptive and nonnociceptive bladder reflexes in cats

2012 ◽  
Vol 302 (9) ◽  
pp. F1090-F1097 ◽  
Author(s):  
Changfeng Tai ◽  
Jeffrey A. Larson ◽  
P. Dafe Ogagan ◽  
Guoqing Chen ◽  
Bing Shen ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Tibial Nerve ◽  
Bladder Capacity ◽  
Saline Infusion ◽  
Saline Control ◽  
Afferent Inhibition ◽  
Urinary Tract Disorders ◽  
Acute Increase ◽  
Nerve Inhibition

Naloxone (an opioid receptor antagonist) was used to examine the role of opioid mechanisms in bladder reflexes and in somatic afferent inhibition of these reflexes by tibial nerve stimulation (TNS). Experiments were conducted in α-chloralose-anesthetized cats when the bladder was infused with saline or 0.25% acetic acid (AA). The bladder volume was measured at the first large-amplitude (>30 cmH2O) contraction during a cystometrogram and termed “estimated bladder capacity” (EBC). AA irritated the bladder, induced bladder overactivity, and significantly ( P < 0.0001) reduced EBC to 14.3 ± 1.9% of the saline control. TNS (5 Hz, 0.2 ms) at 4 and 8 times the threshold (T) intensity for inducing an observable toe movement suppressed AA-induced bladder overactivity and significantly increased EBC to 41.5 ± 9.9% (4T, P < 0.05) and 46.1 ± 7.9% (8T, P < 0.01) of the saline control. Naloxone (1 mg/kg iv) completely eliminated TNS inhibition of bladder overactivity. Naloxone (0.001–1 mg/kg iv) did not change EBC during AA irritation. However, during saline infusion naloxone (1 mg/kg iv) significantly ( P < 0.01) reduced EBC to 66.5 ± 8.1% of the control EBC. During saline infusion, TNS induced an acute increase in EBC and an increase that persisted following the stimulation. Naloxone (1 mg/kg) did not alter either type of inhibition. However, naloxone administered during the poststimulation inhibition decreased EBC. These results indicate that opioid receptors have different roles in modulation of nociceptive and nonnociceptive bladder reflexes and in somatic afferent inhibition of these reflexes, raising the possibility that opioid receptors may be a target for pharmacological treatment of lower urinary tract disorders.

scholarly journals Role of corticosterone in the murine enteric nervous system during fasting

2014 ◽  
Vol 307 (9) ◽  
pp. G905-G913 ◽  
Author(s):  
Katrien Lowette ◽  
Jan Tack ◽  
Pieter Vanden Berghe
Keyword(s):  
Nervous System ◽  
Mrna Expression ◽  
Myenteric Plexus ◽  
Cannabinoid Receptor ◽  
Fine Tuning ◽  
Enteric Neurons ◽  
Neuronal Markers ◽  
Electrical Pulses

Food intake depends on a tightly controlled interplay of appetite hormones and the enteric (ENS) and central nervous system. Corticosterone (CORT) levels, which are mainly studied with regard to stress, are also increased during fasting. However, the role of CORT in the ENS remains elusive. Therefore, we investigated whether CORT modulates activity of enteric neurons and whether its intracellular regulator, 11β-hydroxysteroid dehydrogenase (HSD) type 1, is present in the myenteric plexus, using immunohistochemistry and RT-qPCR. Effects of CORT on neuronal activity and expression of neuronal markers in the myenteric plexus were assessed via Ca2+ imaging and RT-qPCR, respectively, whereas modulations in mixing behavior were measured by video imaging. 11β-HSD-1 was present in enteric neurons along the gastrointestinal tract, and its expression increased after fasting (control: 0.58 ± 0.09 vs. fasted: 1.5 ± 0.23; P < 0.05). CORT incubation significantly reduced neuronal Ca2+ transients in tissues stimulated by electrical pulses (control: 1.31 ± 0.01 vs. CORT: 1.27 ± 0.01, P < 0.01) and in cultured neurons (control: 1.85 ± 0.03 vs. CORT: 1.76 ± 0.03, P < 0.05). CORT decreased small intestinal mixing ( P < 0.05). Incubation of muscle myenteric plexus preparations with CORT induced an increase in cannabinoid receptor 1 (CB1, P < 0.05) and synaptobrevin ( P < 0.05) but not in 11β-HSD-1 mRNA expression. In addition, fasting induced significant elevations in synaptobrevin ( P < 0.05) and CB1 ( P < 0.01) mRNA expression. In conclusion, we suggest CORT to be a downstream factor in a feeding state-related pathway that modulates important proteins in the fine tuning of enteric neurotransmission and gastrointestinal motility.

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