ISOLATION AND MOLECULAR CHARACTERIZATION OF PORCINE CALCITONIN-GENE-RELATED PEPTIDE (CGRP) AND ITS ENDOCRINE EFFECTS IN THE PORCINE PANCREAS

The aim of this study was to investigate the possible role of porcine calcitonin gene-related peptide (CGRP) in the regulation of the endocr ine porcine pancreas. Initially, we isolated and purified CGRP from ex tracts of porcine adrenal glands and pancreases. A single molecular fo rm of the peptide was found in the two tissues. The adrenal peptide wa s sequenced and found to differ from human alpha-CGRP at six positions and from human beta-CGRP at three positions, By immunohistochemistry, CGRP was found in nerve fibers in the pancreatic ganglia. A synthetic replica of the porcine peptide was infused at different dose levels ( 10(-10), 10(-9) and 10(-8) M) into isolated perfused porcine pancreata . With 5 mmol/L glucose in the perfusate, CGRP at 10(-10) and 10(-9) M increased insulin and glucagon secretion, whereas significant decreas es were observed with 10(-8) M, Somatostatin secretion was increased s ignificantly by 10(-8) M CGRP. In immunoneutralization studies (n = 6) using a high-affinity somatostatin antibody, the inhibitory effect of CGRP at 10(-8) M was reversed to a significant stimulation of insulin and glucagon secretion. Insulin secretion in response to square-wave increases in glucose concentration to 11 mM was inhibited dose depende ntly by CGRP; at 10(-8) M the insulin output decreased by 72 +/- 9% (n = 6). The present results indicate that CGRP may be involved in the r egulation of insulin and glucagon secretion from the porcine pancreas.