SUBSTANCE P(6-11) AND NATURAL TACHYKININS INTERACT WITH SEPTIDE-SENSITIVE TACHYKININ RECEPTORS COUPLED TO A PHOSPHOLIPASE-C IN THE RAT URINARY-BLADDER

The rat urinary bladder possesses NK1, NK2 (but not NK3) and 'septide- sensitive' tachykinin receptors coupled to a phospholipase C. The pres ent study performed with SR48968 (10(-6) M) to avoid any interaction o f the tested peptides with NK2 receptors, indicates that substance P(6 -11) (with a high potency), neurokinin A, neurokinin B and to a lesser extent neuropeptide K (with a lower potency) stimulate [H-3]-inositol monophosphate ([H-3]-IP1) formation in this tissue by acting on the ' septide-sensitive' tachykinin receptors. Substance P(6-11) had little affinity for NK1 binding sites and stimulated [H-3]-IP1 formation with an EC50 value and a maxima[ amplitude similar to those of septide. As previously observed with septide, this maximal response of substance P(6-11)) (insensitive to 10(-6) M SR48968) which was about three-fold that of substance P, was blocked by the NK1 receptor antagonist RP6758 0 and prevented by [Pro(9)]substance P (NK, receptor agonist). Similar ly, substance P and several substance P C-terminal fragments prevented the substance P(6-11)-evoked response. In addition, neurokinin A, neu ropeptide K and neurokinin B induced SR48968-resistant responses which exhibited a maximal amplitude similar to that of substance P (6-11) a nd were blocked by RP67580 and totally or partially (neuropeptide K) p revented by [Pro(9)]substance P.