RT Journal Article
SR Electronic
T1 Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 228
OP 234
DO 10.1124/jpet.115.226845
VO 355
IS 2
A1 Zhang, Zhaocun
A1 Slater, Richard C.
A1 Ferroni, Matthew C.
A1 Kadow, Brian T.
A1 Lyon, Timothy D.
A1 Shen, Bing
A1 Xiao, Zhiying
A1 Wang, Jicheng
A1 Kang, Audry
A1 Roppolo, James R.
A1 de Groat, William C.
A1 Tai, Changfeng
YR 2015
UL http://jpet.aspetjournals.org/content/355/2/228.abstract
AB 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.