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 urinary bladder of urethane-anaesthetized rats, with the intravesical volume kept below threshold for activation of the micturition reflex, induced a low amplitude tonic contraction (local, i.e., resistant to ganglionectomy) with high amplitude phasic contractions (reflex, i.e., abolished by ganglionectomy) superimposed. The pharmacology of the local contraction was studied in animals with acute bilateral ablation in the pelvic ganglia: the combined administration of tachykinin NK(1) (S)1-¿2-[3-(3, 4-dichlorophenyl)-1-(3-isopropoxyphenyl-acetyl)-piperidin-3-yl]eth yl¿-4-phenyl-1-azoniabicyclo[2.2.2.]octane chloride (SR 140333) and NK(2) c¿[(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta++ +)¿ (MEN 11420) receptor antagonists (given at doses of 1+0.1 micromol/kg, intravenous (i.v.), respectively) abolished the local bladder contraction induced by topical nociceptin (50 nmol/rat). These results indicate that the topical application of nociceptin onto the bladder evokes a tachykinin-mediated contraction.