title: Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats.
abstract: 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.
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, Peoples Republic of China.|Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Michelle
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Jamie
authors.initials: J
authors.lastname: Uy
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Fuller
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Cameron
authors.initials: C
authors.lastname: Jones
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; and cftai@pitt.edu.|Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
mesh_terms: D019342:Acetic Acid; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002415:Cats; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D005260:Female; D008297:Male; D060525:Pudendal Nerve / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013979:Tibial Nerve / Q000378:metabolism*; D001743:Urinary Bladder / Q000294:innervation*; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D014563:Urodynamics / Q000187:drug effects
chemical_list: D063387:Cannabinoid Receptor Antagonists; D043884:Receptor, Cannabinoid, CB1; D019342:Acetic Acid
keywords: bladder; cannabinoid; neuromodulation; pudendal; tibial