Substance P(6–11) and natural tachykinins interact with septide-sensitive tachykinin receptors coupled to a phospholipase C in the rat urinary bladder

Abstract

The rat urinary bladder possesses NK 1, NK 2 (but not NK 3) and ‘septide-sensitive’ tachykinin receptors coupled to a phospholipase C. The present study performed with SR48968 (10 −6 M) to avoid any interaction of the tested peptides with NK 2 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 [ 3H]-inositol monophosphate ([ 3H]-IP1) formation in this tissue by acting on the ‘septide-sensitive’ tachykinin receptors. Substance P(6–11) had little affinity for NK 1 binding sites and stimulated [ 3H]-IP1 formation with an EC 50 value and a maximal 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 NK 1 receptor antagonist RP67580 and prevented by [Pro 9]substance P (NK 1 receptor agonist). Similarly, substance P and several substance P C-terminal fragments prevented the substance P(6–11)-evoked response. In addition, neurokinin A, neuropeptide K and neurokinin B induced SR48968-resistant responses which exhibited a maximal amplitude similar to that of substance P (6–11) and were blocked by RP67580 and totally or partially (neuropeptide K) prevented by [Pro 9]substance P.