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J. Pharmacol. Exp. Ther. · Nov 2015
Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats.
- Zhaocun Zhang, Richard C Slater, Matthew C Ferroni, Brian T Kadow, Timothy D Lyon, Bing Shen, Zhiying Xiao, Jicheng Wang, Audry Kang, James R Roppolo, William C de Groat, and Changfeng Tai.
- Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.Z., R.C.S., M.C.F., B.K., T.D.L., B.S., Z.X., J.W., A.K., C.T.); Department of Urology, The Second Hospital, Shandong University, Jinan, P.R. China (Z.X.); and the Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.D., C.T.).
- J. Pharmacol. Exp. Ther. 2015 Nov 1; 355 (2): 228-34.
AbstractIn α-chloralose anesthetized cats, we examined the role of opioid receptor (OR) subtypes (µ, κ, and δ) in tibial nerve stimulation (TNS)-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative i.v. doses of selective OR antagonists (cyprodime for µ, nor-binaltorphimine for κ, or naltrindole for δ ORs) was tested. Naloxone (1 mg/kg, i.v., an antagonist for µ, κ, and δ ORs) was administered at the end of each experiment. AA caused bladder overactivity and significantly (P < 0.01) reduced bladder capacity to 21.1% ± 2.6% of the saline control. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement significantly (P < 0.01) restored bladder capacity to 52.9% ± 3.6% or 57.4% ± 4.6% of control, respectively. Cyprodime (0.3-1.0 mg/kg) completely removed TNS inhibition without changing AA control capacity. Nor-binaltorphimine (3-10 mg/kg) also completely reversed TNS inhibition and significantly (P < 0.05) increased AA control capacity. Naltrindole (1-10 mg/kg) reduced (P < 0.05) TNS inhibition but significantly (P < 0.05) increased AA control capacity. Naloxone (1 mg/kg) had no effect in cyprodime pretreated cats, but it reversed the nor-binaltorphimine-induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pretreated cats. These results indicate a major role of µ and κ ORs in TNS inhibition, whereas δ ORs play a minor role. Meanwhile, κ and δ ORs also have an excitatory role in irritation-induced bladder overactivity. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
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