Effects of calcitonin gene-related peptide on somatostatin and gastrin gene expression in rat antrum.
The ability of exogenous calcitonin gene-related peptide (CGRP) to regulate gastric somatostatin and gastrin messenger RNA was studied in vitro in rat antral mucosal/submucosal tissues. Somatostatin and gastrin mRNA were quantified by Northern and dot blot hybridization and regulatory peptides were measured by radioimmunoassay. Incubation of antral tissues in the presence of CGRP [1 x 10(-7) M] for 60 min resulted in a reciprocal increase in somatostatin and a decrease in gastrin release: 214.7+/-28.5 vs. control of 81.7+/-5.9 pg somatostatin per gram of tissue and 2.2+/-0.3 vs. control of 5.5+/-0.7 ng gastrin per gram of tissue (P < 0.001). CGRP caused parallel changes in somatostatin and gastrin mRNA levels: somatostatin mRNA increased by 212% from 0.40+/-0.02 to 1.25+/-0.09 absorbance units (AU) (P < 0.001) and gastrin mRNA decreased by 73% from 0.55+/-0.08 to 0.15+/-0.02 AU (P < 0.001). Somatostatin monoclonal antibody prevented CGRP-mediated inhibition of both gastrin release and gastrin mRNA levels. In conclusion, CGRP is capable of modulating both the secretion and gene expression of regulatory peptides from antral G and D cells. Somatostatin immunoneutralization studies suggest that the actions of CGRP on gastrin release and gene expression are indirect and mediated through the paracrine influences of somatostatin.
Ren
J
J
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Dunn
S T
ST
Tang
Y
Y
Wang
Y
Y
Gao
J
J
Brewer
K
K
Harty
R F
RF
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D005755:Gastrins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D011706:Pyloric Antrum / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000235:genetics*
D005755:Gastrins; D012333:RNA, Messenger; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide