Calcitonin gene-related peptide occurs in intrapancreatic nerves and endocrine cells. The peptide is therefore a candidate for being of physiological importance for pancreatic function. We examined the direct effects of calcitonin gene-related peptide on islet hormone secretion in the pig by infusing the peptide into the superior pancreatic artery. We found that 15 min intrapancreatic infusion of calcitonin gene-related peptide (22 pmol/min) decreased baseline pancreatic insulin output from 48 +/- 10 microU/min to 8 +/- 7 microU/min (p less than 0.01). Moreover, calcitonin gene-related peptide inhibited glucose-induced insulin secretion by 45% compared to controls (p less than 0.01), yet left terbutaline (beta 2-adrenoceptor)-stimulated insulin secretion unaffected. Furthermore, while being without effect on baseline glucagon output, calcitonin gene-related peptide potentiated terbutaline-induced glucagon secretion more than seven-fold (p less than 0.001). In contrast, the peptide did not affect baseline or stimulated pancreatic somatostatin output. We conclude that in pigs calcitonin gene-related peptide inhibits insulin secretion and potentiates glucagon secretion by direct effects on the pancreas that are not mediated by primary alterations in pancreatic somatostatin secretion. We suggest that the neuropeptide calcitonin gene-related peptide might be of importance for the intrapancreatic regulation of insulin and glucagon secretion in pigs.