A modulating role of prostaglandins in contractions of the guinea-pig ileum.

1 The role of prostaglandins in contractions of the guinea-pig ileum evoked either directly by acetylcholine or indirectly by angiotensin and by coaxial stimulation has been investigated.2 Prostaglandin E(2) in low concentration (6 nM) slightly augmented both types of contraction. Indomethacin, an inhibitor of prostaglandin synthesis, markedly reduced the indirectly evoked contractions but did not affect contractions in response to acetylcholine. The addition of prostaglandin E(2) to the preparation treated previously with indomethacin restored the effect of indirect stimulation.3 The pretreatment of the preparation with guanethidine or alpha-methyl-p-tyrosine prevented the inhibitory effect of indomethacin on indirectly evoked contractions. Prostaglandin E(2) addition to such preparations considerably augmented both types of contraction.4 The stimulation of non-cholinergic, non-adrenergic inhibitory nerves in the taenia coli and ileum preparations evoked hyperpolarization and relaxation of the preparations followed by action potentials and contraction. These responses were not changed by indomethacin pretreatment and prostaglandin E(2), but rebound contraction was sometimes augmented by the prostaglandin.5 Two mechanisms for the effects of prostaglandin E(2) are suggested: a direct effect on smooth muscle, and an indirect action through the sympathetic nerves which by release of noradrenaline affect the acetylcholine release from parasympathetic nerve endings.