The Pituitary Adenylate Cyclase Activating Polypeptide Type 1 Receptor (PAC₁‐R) Is Expressed on Gastric ECL Cells: Evidence by Immunocytochemistry and RT‐PCR

Abstract

The current study was undertaken to determine the presence and distribution of PAC1-Rs within the gastric mucosa. Polyclonal antibodies to the carboxyl terminus of the rat PAC1-R were generated and shown to be specific against the PAC1-R expressed in NIH 3T3 cells. Western blot analysis using isolated (approximately 85% pure) ECL cell membranes identified a 48 kD protein consistent with the calculated molecular mass of the cloned PAC1-R. RT/PCR performed using specific primers for the PAC1-R confirmed the presence of splice variants of the rat PAC1-R, but not VPAC1-R or VPAC2-R. These data provide the first direct evidence for the existence of functional PACAP Type I receptors on ECL cells of the gastric mucosa and suggest a potential role for PACAP in the stimulation of gastric acid secretion and in the regulation of the growth of ECL cells.

Histamine Mediates the Stimulatory Action of Ghrelin on Acid Secretion in Rat Stomach

“…Another transmitter, PACAP, was also found to increase histamine release from ECL cells [29]. PACAP-immunoreactive nerve fibers are abundant in the gastric mucosa of both rat and humans [30] and gastric ECL cell possesses PACAP receptors (PAC1) [31]. Gastrin is now known as major stimulants of histamine release from gastric ECL cell [32].…”

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

“…The experimental data presented above show that PACAP is a functional ligand on the rat ECL cell surface. Western analysis has shown the presence of PAC1 in ECL cell membranes (26), and there is, in this cell type, expression of all the splice variants of PAC1, as demonstrated by RT-PCR. No VPAC1 or VPAC2 was detected with any of the primers, which were selected to span intron-exon junctions (primers that prevent spurious signals from genomic DNA).…”

Ghrelin and gastric acid secretion

“…Another transmitter, PACA, was also found to increase histamine release from ECL cell [24] . PACAP-immunoreactive nerve fibers are abundant in the gastric mucosa of both rat and humans [25] and gastric ECL cells possesses PACAP receptors(PAC1) [26] . Gastrin is now known as major stimulant of histamine release from gastric ECL cells [27] .…”

“…Comparing the secretion of ghrelin with that of gastrin, the secretion of gastrin is induced by food intake [26] , while the secretion of ghrelin is increased during fasting period [33] . As described above, there are many differences between gastrin and ghrelin in the actions, their roles may be different.…”