Role of PACAP1 receptor in regulation of ECL cells and gastric acid secretion by pituitary adenylate cyclase activating peptide.
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.
Pisegna
J R
JR
CURE: VA/UCLA Digestive Diseases Research Center, West LA VA Medical Center, Department of Physiology and Medicine, California, USA. jpisegna@ucla.edu
Ohning
G V
GV
Athmann
C
C
Zeng
N
N
Walsh
J H
JH
Sachs
G
G
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*
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