Prostaglandin E2 and [14C]arachidonic acid release by carbachol in the isolated canine parietal cell

Abstract

Parietal cells have the capacity to synthesize prostaglandins (PGs) and these PGs have a significant effect on parietal cell acid secretion. We examined the stimuli responsible for the control of PG production by parietal cells. Two approaches were utilized. One consisted of measuring PGE2 concentration in the incubation media containing dispersed canine parietal cells stimulated with increasing concentrations of carbachol, histamine plus a phosphodiesterase inhibitor and pentagastrin. PGE2 was measured by radioimmunoassay. The other consisted of measuring the release of radioactive arachidonic acid by parietal cells prelabeled with [4C]arachidonic acid to increasing concentrations of the secretagogues. Both techniques gave very similar results. Only carbachol stimulated the release of PGE2 as well as [14C]arachidonic acid into the incubation media. The increase in PGE2 release was from a base line of 44.3 +/- 10.8 pg/ml to 51.0 +/- 11.7, 55.2 +/- 11.1 and 69.3 +/- 14.3 pg/ml at carbachol concentrations of 10(-6), 10(-5) and 10(-4) M, respectively. In prelabeled cells, carbachol stimulated 1072 +/- 141 and 1264 +/- 155 cpm/ml above basal at concentrations of 10(-5) and 10(-4) M, respectively. Neither histamine nor pentagastrin stimulated PGE2 or [14C]arachidonic acid release significantly at any concentration. The effect of carbachol on the release of [14C]arachidonic acid was blocked by atropine and the exclusion of calcium from the incubation media. Our data suggest that the cholinergic tone to the stomach with subsequent interaction of acetylcholine with muscarinic receptors determines the amount of PG production by the parietal cells. Prostaglandins may then modulate acid secretion by limiting the combined, potentiated effects of the secretagogues.