Effect of thiorphan on tachykinin-induced potentiation of nerve- mediated contractions of the rat isolated vas deferens

R Patacchini, CA Maggi, P Rovero, D Regoli, G Drapeau and A Meli

Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.

We have assessed the ability of thiorphan, an inhibitor of enkephalinase, to influence the potentiation of the nerve-mediated contractions of the rat isolated vas deferens (pars prostatica) by mammalian tachykinins [substance P, (SP); neurokinin A (NKA); and neurokinin B (NKB)] and selective tachykinin agonists. In the absence of thiorphan, the rank order of potency of mammalian tachykinins was NKA greater than NKB much greater than SP. The maximal response to SP did not exceed 40% of that to NKA or NKB. Thiorphan (10 microM) had no effect on twitches per se, but increased the potency and maximum effect of mammalian tachykinins. [Pro9]-SP sulfone, a selective NK-1 receptor agonist had no effect, either in the absence or presence of thiorphan. [MePhe7]-NKB had some potentiating effect, but only at micromolar concentrations. [Nle10]-NKA (4-10) and [beta-Ala8]-NKA (4-10), two selective NK-2 agonists displayed good activity. [Nle10]-NKA (4-10) was potentiated by thiorphan. On the other hand, the action of [beta Ala8]- NKA (4-10) was completely thiorphan-resistant. These findings indicate that estimate of activity of tachykinins and tachykinin related peptides in this bioassay is influenced markedly by peptide degradation via a thiorphan-sensitive mechanism. NK-2 receptors are the main if not the sole mediators of the response to tachykinins in this bioassay organ.

Volume 250, Issue 2, pp. 678-681, 08/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				J. M. Goldhill, T. Shea-Donohue, N. Ali, and V. M. Piñeiro-Carrero Tachykinergic Neurotransmission Is Enhanced in Small Intestinal Circular Muscle in a Rabbit Model of Inflammation J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1373 - 1378. [Abstract] [Full Text]