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 bl adder contractions was determined in urethane-anaesthetized rats with intact bladder innervation and in animals with acute, bilateral ablati on of pelvic ganglia. In addition, tachykinin receptors mediating the response to the agonists were characterized by means of the non-peptid e NK1 and NK2 receptor selective antagonists, RP 67 580 and SR 48 968 respectively. In both experimental conditions (normal and ganglionecto mized), the three tachykinin agonists induced a dose-dependent increas e in intravesical pressure, however reflex bladder contractions were p roduced by the agonists only in animals with intact bladder innervatio n. 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 effec ts 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 a nimals 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 (1 0 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 N K1 receptors, respectively.