PACAP type I receptor activation regulates ECL cells and gastric acid secretion

Pituitary adenylate cyclase activating polypeptide (PACAP) is present in ga stric nerves, and PACAP receptors (PAC1) are found on gastric enterochromaf fin-like (ECL) cells. Expression of PAC1 splice variants in purified ECL ce lls was determined by RT-PCR. PACAP effects on ECL cells were analyzed by v ideo imaging of [Ca2+](i) and histamine release; its effects on gastric gla nds were examined by confocal microscopy of [Ca2+](i) in ECL and parietal c ells. PACAP action on D cells was measured by [Ca2+](i) and radioimmunoassa y. PACAP effects on acid secretion were determined in fistula rats with or without neutralizing anti-somatostatin antibodies. All splice variants of P AC1 were found, but vasoactive intestinal polypeptide (VIP) receptor (VPAC) products were absent. PACAP-27 and -38 dose-dependently raise [Ca2+](i) in ECL cells and stimulate histamine release. VIP had a much lower affinity, which demonstrates the presence of PAC1 but not VPAC. PACAP elevated [Ca2+] (i) in ECL and parietal cells of superfused gastric glands, but only the pa rietal cell signal was inhibited by ranitidine, showing the absence of PAC1 on parietal cells and demonstrating functional coupling between the cell t ypes. PACAP and VIP stimulated calcium signaling and somatostatin release f rom D cells with almost equal efficacy. Acid secretion was stimulated after intravenous injection of PACAP into rats treated with somatostatin antibod y. PACAP is a candidate as a mediator of neural regulation of acid secretio n.