Comparison of potency of substance P and related peptides on [3H]-acetylcholine release, and contractile actions, in the guinea-pig ileum.

A range of tachykinins including substance P were studied for their ability to contract the guinea-pig ileum longitudinal muscle preparation on brief exposure (20S) to the peptides, and their ability to evoke the release of [3H]-acetylcholine (ACh) from previously labelled stores within the myenteric plexus. With respect to their immediate spasmogenic activity, none of the peptides differed greatly in potency from substance P. Atropine did not modify the response to the tachykinins suggesting that the release of ACh does not contribute to the contraction resulting from brief exposure to the peptides. In the release studies, all tachykinins used produced a dose-related, calcium-dependent release of [3H]-ACh but the differences in potency were much greater. Eledoisin was the most potent and its evoked release of ACh was unaffected by hyoscine, hexamethonium, guanethidine and naloxone suggesting the release is not mediated via, or modulated by, opiate or autonomic neuronal influences. The two orders of tachykinin potency found suggest that the two processes, initial contraction and ACh release, may be principally mediated via two distinct subclasses of substance P receptor designated SP-P and SP-E respectively.