title: Role of PACAP1 receptor in regulation of ECL cells and gastric acid secretion by pituitary adenylate cyclase activating peptide.
abstract: We previously reported that PAC1 is expressed on ECL cells resulting in stimulation of [Ca2+]i, histamine and acid secretion. The study reported here characterized the signaling by PAC1 on ECL cells; determined the effects of PACAP on the gastric acid secretion in vivo, and determined the effects of chronic administration of PACAP-27 on ECL cell proliferation. PACAP-27 dose dependently stimulated ECL cell Ca2+ and AC with detectable stimulation at 1 nM and maximal stimulation at 100 nM (six-fold). In rats PACAP-27 administration (10 pmol/kg/h) increased the rate of gastric acid secretion when an antisomatostatin antibody was co-administered. Chronic administration of PACAP (10 pmol/h for seven days) via osmotic pump resulted in a more than twofold increase in BrdU incorporation into ECL cells. PACAP acting at the PAC1 results in dual signaling responses to both [Ca2+]i. AC in ECL cells stimulates gastric acid secretion via the actions of histamine acting at the parietal cell and in whole animals leads to proliferation of ECL cells when administered chronically.
authors.affiliation: CURE: VA/UCLA Digestive Diseases Research Center, West LA VA Medical Center, Department of Physiology and Medicine, California, USA. jpisegna@ucla.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Pisegna
authors.forename: G V
authors.initials: GV
authors.lastname: Ohning
authors.forename: C
authors.initials: C
authors.lastname: Athmann
authors.forename: N
authors.initials: N
authors.lastname: Zeng
authors.forename: J H
authors.initials: JH
authors.lastname: Walsh
authors.forename: G
authors.initials: G
authors.lastname: Sachs
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019861:Enterochromaffin-like Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009479:Neuropeptides / Q000494:pharmacology* / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000502:physiology*
chemical_list: C495403:Adcyap1 protein, rat; C495505:Adcyap1r1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D000262:Adenylyl Cyclases