MECHANISM OF ACTION OF SUBSTANCE-P IN GUINEA-PIG ILEUM LONGITUDINAL SMOOTH-MUSCLE - A REEVALUATION

1. A proposed mechanism of contractile action of substance P in guinea‐pig ileum longitudinal smooth muscle involving a decrease in membrane K+ permeability (PK) has been re‐examined. 2. Potentiation of responses to substance P by the K+ channel blocker tetraethylammonium (TEA) was originally proposed as evidence for a mechanism of action of substance P involving a decrease in PK. Potentiation was confirmed; however this was found not to be specific to substance P since a similar potentiation of responses was seen with agonists not thought to act via a decrease in PK. 3. Antagonism of contractile responses to substance P by noradrenaline was similarly confirmed. However, this antagonism was found to represent a non‐specific functional interaction through the inhibitory actions of beta‐adrenoceptors rather than the proposed specific interaction with an increase in PK by noradrenaline which is normally alpha 1‐adrenoceptor mediated. 4. Experiments were made measuring 86Rb efflux, in depolarized guinea‐pig ileum longitudinal smooth muscle, to estimate PK. These studies confirmed a reported decrease in PK with TEA, but failed to detect the previously reported decrease with substance P. 5. These results, although not disproving a suggested mechanism of direct contractile action of substance P in guinea‐pig ileum longitudinal smooth muscle involving a decrease in PK, do throw doubt on either the evidence, or its interpretation, as proposed by the original authors in support of such a mechanism. © 1990 The Physiological Society