IN-VIVO EFFECTS OF NEUROKININ-B ON RAT URINARY-BLADDER MOTILITY - INVOLVEMENT OF TACHYKININ-NK1 AND TACHYKININ-NK2 RECEPTORS

The ability of the selective tachykinin NK1 and NK2 receptor agonists, [Sar(9)] substance P (SP) sulfone and [beta Ala(8)] neurokinin A (NKA), (4-10) 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 NK1 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 mu mol/kg, i.v.) reduced the response to [Sar(9)] SP sulfone (50 pmol/rat) in both preparations without modifying the effects induced by the NK2 receptor agonist. On the other hand, SR 48 968 (1 mu mol/kg, i.v.) antagonized responses induced by [beta Ala(8)] NKA (4-10) (50 pmol/rat) but not those evoked by [Sar(9)] SP sulfone. In animals with intact urinary bladder innervation, the effect of NKB (50 pmol/rat) was inhibited by SR 48 968 (1 mu mol/kg, i.v.) 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 (10 mu mol/kg, i.v.) but not by SR 48 968. We conclude that NKB induces reflex and direct bladder muscle contractions by stimulating NK2 and NK1 receptors, respectively.