Neuropeptides (1994) 27, 53-62 0 Longman Group Ltd 1994 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA In vivo Effects of Neurokinin B on Rat Urinary Bladder Motility: Involvement of Tachykinin NK, and NK, Receptors A. LECCI, S. GIULIANI, S. MEINI and C. A. MAGGI Pharmacology zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Research Department, ‘A. Menarini’ Pharmaceuticals, via Sette santi 3, 50131 Florence, Italy (Reprint requests to ALI Abstract-The ability of the selective tachykinin NK, and NK2 receptor agonists, [Sargl substance P (SP) sulfone and [/3Ala*] neurokinin A (NKA),“’ respectively, and neurokinin B (NKB) to stimulate urinary bladder contractions was determined in urethane-anaesthetized rats with intact bladder innervation and in animals with acute, bilateral ablation of pelvic ganglia. In addition, tachykinin receptors mediating the response to the agonists were characterized by means of the non-peptide NK, and NK2 receptor selective antagonists, RP 67 580 and SR 48 968 respectively. In both experimental conditions (normal and ganglionectomized), the three tachykinin agonists induced a dose-dependent increase in intravesical pressure, however reflex bladder contractions were produced by the agonists only in animals with intact bladder innervation. RP 67 580 (10 PmoVkg, i.v.) reduced the response to [Sar’] SP sulfone (50 pmol/rat) in both preparations without modifying the effects induced by the NK, receptor agonist. On the other hand, SR 48 968 (I pmol/kg, i.v.) antagonized responses induced by [flAla*l NKA”” (50 pmol/rat) but not those evoked by [Sargl SP sulfone. In animals with intact urinary bladder innervation, the effect of NKB (50 pmol/rat) was inhibited by SR 48 968 (1 pmol/kg, i.v.1 but not by RP 67 580; on the contrary, in rats with ablation of pelvic ganglia, the direct bladder contraction induced by NKB was reduced by RP 67 580 (IO pmol/kg, i.v.) but not by SR 48 968. We conclude that NKB induces reflex and direct bladder muscle contractions by stimulating NK, and NK, receptors, respectively. Introduction Met-NH,. Tachykinins, mostly substance P (SP) Tachykinins are a family of peptides sharing the common C-terminal sequence Phe-X-Gly-Leu- and neurokinin A (NKA), are present in the rat urinary bladder and several studies indicate that these peptides could have a role in the neu- rotransmission or neuromodulation of this organ Date received 13 December 1993 Date accepted 9 February 1994 (see ’ for review). The biological effects of tachy- kinins are mediated by three different receptors 53