PAC1 deficiency in a murine model induces gastric mucosa hypertrophy and higher basal gastric acid output.
Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion.
Lu
Yuxin
Y
Division of Gastroenterology and Hepatology, Veterans Administration Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
Germano
Patrizia
P
Ohning
Gordon V
GV
Vu
John P
JP
Pisegna
Joseph R
JR
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology*; D005755:Gastrins / Q000097:blood / Q000235:genetics; D006984:Hypertrophy / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000172:deficiency* / Q000235:genetics
D015415:Biomarkers; D005755:Gastrins; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G997-G1003
11557520
Ann N Y Acad Sci. 1998 Dec 11;865:147-56
9928007
Biochem Biophys Res Commun. 1989 Oct 16;164(1):567-74
2803320
Ann N Y Acad Sci. 2006 Jul;1070:399-404
16888199
Eur J Anaesthesiol. 1989 Jul;6(4):265-79
2759065
J Clin Invest. 1999 Nov;104(10):1383-91
10562300
Neuroscience. 1992;46(2):439-54
1542417
Mol Cell Endocrinol. 2005 Feb 28;231(1-2):49-63
15713535
Peptides. 2007 Sep;28(9):1688-99
17606312
Br J Pharmacol. 2004 May;142(1):67-78
15023860
Regul Pept. 2002 May 30;105(3):145-54
11959368
Physiol Genomics. 2005 Mar 21;21(1):81-91
15613615
J Mol Neurosci. 2005;26(1):85-97
15968088
Gastroenterology. 1997 Sep;113(3):1015-25
9287997
Gastroenterology. 1999 Mar;116(3):623-35
10029621
J Physiol. 2001 Sep 15;535(Pt 3):663-77
11559765
J Clin Invest. 2000 May;105(9):1307-15
10792006
Am J Physiol Gastrointest Liver Physiol. 2004 Jan;286(1):G51-9
12816760
Endocrinology. 2008 Feb;149(2):498-505
17974627