Arachidonic acid-induced secretion in the rat colon. Indomethacin-resistant neuronal and epithelial actions.

The effect of arachidonic acid on short-circuit current (Isc) was studied in two preparations of the rat colon descendens, one with and one without the submucosal plexus. In both preparations, arachidonic acid (10(-7)-5 x 10(-5) mol.l-1) increased Isc concentration-dependently. The cyclooxygenase blocker, indomethacin, inhibited its action only partially. The lipoxygenase inhibitor, nordihydroguaiaretic acid, was an ineffective inhibitor of the response to arachidonic acid. Tetrodotoxin (TTX), atropine, and hexamethonium blocked the effect of arachidonic acid in the preparation with the submucosal plexus. Inhibition by neuronal blockers was also observed in the presence of indomethacin. After removal of the submucosal plexus, TTX no longer affected the Isc response evoked by arachidonic acid. This epithelial action of arachidonic acid was inhibited by the calmodulin antagonist, trifluoperazine, and the intra-cellular Ca2(+)-antagonist, TMB-8. Inhibition by these drugs was also found in the presence of indomethacin. Consequently, for the secretion induced by arachidonic acid two sites of action, the submucosal plexus and the epithelium, and two mechanisms of action, prostaglandin-mediated and non-mediated, could be distinguished.