Abstract
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 (1×10 −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.
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