Tachykinin-mediated effect of nociceptin in the rat urinary bladder in vivo

The application of nociceptin (5-50 nmol/rat) onto the serosa in the urinar y bladder of urethane-anaesthetized rats, with the intravesical volume kept below threshold for activation of the micturition reflex, induced a low am plitude tonic contraction (local, i.e., resistant to ganglionectomy) with h igh amplitude phasic contractions (reflex, i.e., abolished by ganglionectom y) superimposed. The pharmacology of the local contraction was studied in a nimals with acute bilateral ablation in the pelvic ganglia: the combined ad ministration of tachykinin NK1 (S)1-{2-[3-(3,4-dichlorophenyl)-1-(3-isoprop oxyphenyl-acetyl)-piperidin-3-yl]ethyl}-4-phenyl-1- azoniabicyclo[2.2.2.]oc tane chloride (SR 140333) and NK2 c{[(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu ]c(2 beta-5 beta)} (MEN 11420) receptor antagonists (given at doses of 1 0.1 mu mol/kg, intravenous (i.v.), respectively) abolished the local bladde r contraction induced by topical nociceptin (50 nmol/rat). These results in dicate that the topical application of nociceptin onto the bladder evokes a tachykinin-mediated contraction. (C) 2000 Elsevier Science B.V. All rights reserved.