Evidence for a role in stimulus--secretion coupling of prostaglandins derived from release of arachidonoyl residues as a result of phosphatidylinositol breakdown.

Abstract

Mouse pancreases were prelabeled with [14C]arachidonic acid in the presence of the secretogogue carbamoylcholine. They were then incubated in media containing atropine and 1% albumin. The atropine causes the tissue to revert to the resting state, and the albumin binds free [14C]arachidonic acid. The tissues were finally incubated in media containing no stimulant or the stimulant cerulein, which is not blocked by atropine. Stimulation with cerulein led to a 44% loss of [1-14C]arachidonic acid from phosphatidylinositol. About half of this released arachidonic acid ended up in phosphatidic acid. The remainder of the loss could not be accounted for in any other lipid. No other phospholipids showed statistically significant changes on stimulation. Several lines of evidence indicated that the missing arachidonic acid was converted to prostaglandins [PG], which play a role in stimulus-secretion coupling. Four nonsteroidal anti-inflammatory drugs inhibited secretogogue-induced amylase secretion from pancreases, and their potencies paralleled their potencies in inhibiting cyclooxygenase, which converts arachidonic acid to PG. Amylase secretion was stimulated by arachidonic acid, and this stimulation was blocked by the nonsteroidal antiinflammatory drug indomethacin. Other fatty acids failed to elicit amylase secretion. At concentrations of 3-10 nM, PGI2 PGE, PGE2, PGD2 and PGF2.alpha. gave statistically significant stimulations of secretion. Other PG tested gave no significant stimulation.