Contribution of endogenous prostaglandins to excitation of the myenteric plexus of guinea-pig ileum: are adrenergic factors involved?

The role of endogenous prostaglandins (PGs) in the nicotine-induced contraction and release of ACh was investigated in the isolated guinea-pig ileum. A low concentration of indomethacin (IND 2.8 microM) inhibited the contraction and ACh release induced by nicotine. These inhibitory effects of IND were reversed by PGE2 at concentrations which are thought to be released spontaneously. SC-19220, a PG receptors antagonist, also inhibited the contraction and ACh release induced by nicotine. Unlike the nicotine-induced release of ACh, the potassium-induced release of ACh was unaffected by IND and SC-19220. IND was as potent in inhibiting the responses to cholinergic nerve stimulation by nicotine after treatment of the preparations with antiadrenergic agents. It is concluded that the inhibitory effect of IND does not depend on the functional integrity of adrenergic neurons and that endogenous PGs contribute directly to the modulation of myenteric plexus excitability by nicotine.