Nociceptin and the micturition reflex.
The i.v. administration of nociceptin (10-100 nmol/kg) inhibits the micturition reflex in a naloxone-resistant manner. The effects induced by i.v. nociceptin were not observed in capsaicin-pretreated animals indicating that i.v. nociceptin inhibits the micturition reflex by inhibiting afferent discharge from capsaicin-sensitive nerves. Supporting this interpretation, nociceptin also inhibited the reflex but not the local bladder contraction induced by topical capsaicin and protects this reflex (but not the local contraction) by desensitization. Intrathecal nociceptin (10 nmol/rat) produces urodynamic modifications similar to those induced by the i.v. administration. Intracerebroventricular (i.c.v.) administration of nociceptin (0.3-1 nmol/rat) also inhibited the micturition reflex in a naloxone-resistant manner suggesting a direct effect on supraspinal sites controlling the micturition. Beyond the inhibitory effects exerted by nociceptin on the micturition reflex, a peripheral excitatory effect mediated by capsaicin-sensitive fibers was also detected. The application of nociceptin (5-50 nmol/rat) onto the bladder serosa when the intravesical volume was subthreshold for the triggering of the micturition reflex, activated the reflex in a dose-dependent manner; the same treatment produced a biphasic effect on the ongoing reflex. In addition to the triggering of micturition reflex, topical nociceptin evokes a local tonic-type contraction that was abolished by the coadministration of tachykinin NK(1) and NK(2) receptor antagonists. Altogether these results indicate that ORL(1) receptors are present at several sites for the integration of the micturition reflex, and that their activation may produce both excitatory or inhibitory effects, depending on the route of administration and the experimental conditions.
Lecci
A
A
Pharmacology Department, Menarini Ricerche, via Sette Santi 3, 50131, Florence, Italy.
Giuliani
S
S
Meini
S
S
Maggi
C A
CA
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007700:Kinetics; D008954:Models, Biological; D009420:Nervous System / Q000187:drug effects*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002211:Capsaicin; D018847:Opioid Peptides; D011957:Receptors, Opioid; D018039:Receptors, Tachykinin; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat