PACAP type I receptor activation regulates ECL cells and gastric acid secretion
Ningxin Zeng, … , George Sachs, Joseph R. Pisegna
Ningxin Zeng, … , George Sachs, Joseph R. Pisegna
Published November 15, 1999
Citation Information: J Clin Invest. 1999;104(10):1383-1391. https://doi.org/10.1172/JCI7537.
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Article

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

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is present in gastric nerves, and PACAP receptors (PAC1) are found on gastric enterochromaffin-like (ECL) cells. Expression of PAC1 splice variants in purified ECL cells was determined by RT-PCR. PACAP effects on ECL cells were analyzed by video imaging of [Ca2+]i and histamine release; its effects on gastric glands were examined by confocal microscopy of [Ca2+]i in ECL and parietal cells. PACAP action on D cells was measured by [Ca2+]i and radioimmunoassay. PACAP effects on acid secretion were determined in fistula rats with or without neutralizing anti-somatostatin antibodies. All splice variants of PAC1 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 stimulated 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 parietal cell signal was inhibited by ranitidine, showing the absence of PAC1 on parietal cells, and demonstrating functional coupling between the cell types. PACAP and VIP stimulated calcium signaling and somatostatin release from D cells with almost equal efficacy. Acid secretion was stimulated after intravenous injection of PACAP into rats treated with somatostatin antibody. PACAP is a candidate as a mediator of neural regulation of acid secretion.

Authors

Ningxin Zeng, Christoph Athmann, Tao Kang, Rong-Ming Lyu, John H. Walsh, Gordon V. Ohning, George Sachs, Joseph R. Pisegna

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Figure 1

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RT-PCR of ECL-cell and parietal-cell RNA. (a) RT-PCR performed on ECL ce...
RT-PCR of ECL-cell and parietal-cell RNA. (a) RT-PCR performed on ECL cell RNA using primers specific to the third intracellular loop splice variants. Sense primers (S1, HipS, HOPS, SV3AS) were used together with antisense primers (S1, HipS, HOPS, SV3AS) that spanned the intron-exon junctions as described previously (23). Amplification using primers for β-actin was performed as a control and is shown in the last lane. (b) RT-PCR performed on purified ECL and parietal cells (PC). The primers used were designed to amplify PAC1, histidine decarboxylase (HDC), H,K-ATPase, and β-actin in these 2 purified cell preparations (>85%).