Block of electrically induced contractions of guinea pig longitudinal muscle by prostaglandin synthetase and receptor inhibitors.

Inhibitors of prostaglandin synthetase as well as prostaglandin receptor inhibitors block electrically induced contractions of the longitudinal muscle of the guinea pig ileum. This blockade is selectivety reversed by some prostaglandins, particularly those of the E series. There is a very close parallel between the potency with which the synthetase inhabitors block transmission and inhibit the enzyme. That blockade is actually accompanied by inhibition of synthesis of PG was shown by inhibition of arachidonic acid contractions of the tissue by indomethacin. The inhibition of transmission by indomethacin involves block of acetylcholine release as shown by direct assay and by the fact that physostigmine can reverse the block. Physostigmine also reverses block of transmission by prostaglandin receptor inhibitors and by morphine but not that produced by chlorpromazine or papaverine. Other evidence for a presynaptic site of action for the synthetase and PG receptor inhibitors is indicated by lack of effect of blocking concentrations on response of the tissue to exogenous acetylcholine. That prostaglandin reverses block of transmission by a presynaptic effect was shown by lack of reversal of atropine and papaverine inhibition of electrically induced contractions; both of these drugs produce this effect directly on the smooth muscle. These results are compatible with the previous postulate that a prostaglandin system, comprised of prostaglandin, its synthesizing enzyme and its receptor, is directly involved with the release of acetylcholine in the ileum.