Role of µ, κ, and δ opioid receptors in tibial inhibition of bladder overactivity in cats.
In 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.
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.).
Zhaocun
Z
Zhang
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.).
Richard C
RC
Slater
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.).
Matthew C
MC
Ferroni
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.).
Brian T
BT
Kadow
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.).
Timothy D
TD
Lyon
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.).
Bing
B
Shen
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.).
Zhiying
Z
Xiao
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.).
Jicheng
J
Wang
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.).
Audry
A
Kang
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.).
James R
JR
Roppolo
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.).
William C
WC
de Groat
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.) cftai@pitt.edu.
Changfeng
C
Tai
D019342:Acetic Acid; D000818:Animals; D002415:Cats; D005260:Female; D008297:Male; D009019:Morphinans / Q000494:pharmacology / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013979:Tibial Nerve; D004561:Transcutaneous Electric Nerve Stimulation; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*
D009019:Morphinans; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C058450:cyprodime; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C055382:naltrindole; D019342:Acetic Acid