Porcine ileal polypeptide causes an increase in cytoplasmic Ca 2+ in both parietal and chief cells resulting in acid and pepsinogen secretion

Abstract

Porcine ileal polypeptide, an enterooxyntin isolated from distal small intestinal mucosal epithelium, has been observed to stimulate gastric acid secretion in vivo as well as in vitro (Wider, M.D. et al. (1984) Endocrinology 115, 1484–1491, Wider M.D. et al. (1986) Endocrinology 118, 1546–1550). We report here that porcine ileal polypeptide stimulates both acid (aminopyrine accumulation) and pepsinogen secretion in isolated, enriched populations of guinea pig parietal and chief cells in a dose-dependent manner. Further, 10 −9 M porcine ileal polypeptide caused an increase in cytoplasmic Ca 2+ concentration in both parietal and chief cells similar in magnitude to that observed with gastrin-17 (10 −8 M) (as measured by both fura-2 and aequorin) and cholecystokinin octapeptide (CCK-OP) (10 −8 M), respectively. Procine ileal polypeptide has been observed to cause no stimulation of cAMP production ing astric glands from guinea pigs (Gespach, C., personal communication) nor is there any effect of medium Ca 2+ depletion on acid production observed with guinea pig gastric mucosal sections. It is concluded that porcine ileal polypeptide, at concentrations similar to circulating levels observed in plasma of normal pigs (5 · 10 −9 M), acts directly on the parietal and chief cells to cause the mobilization of intracellular Ca 2+ from the stores resulting in acid and pepsinogen secretion. These experiments demonstrate that this peptide is a potent entoerroxyntin and chief cell secretagogue which acts via the same signal transduction mechanisms as gastrin and cholecystokinin.