Effect of calcitonin gene-related peptide (CGRP) on motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused porcine antrum

We studied the effect of porcine CGRP (pCGRP) in concentrations from 10(-10 ) to 10(-8) mol L-1 on the motility and on the release of substance P, neur okinin A, somatostatin and gastrin in the antrum using the isolated perfuse d porcine antrum as experimental model. In addition, we studied the localiz ation of CGRP by immunohistochemistry in the porcine antrum, CGRP-immunorea ctive nerve fibres were found mainly in the submucous layer and in the exte rnal muscle coat, where they were seen in all layers, and in the ganglia of the myenteric nervous plexus. The frequency of contraction was significant ly and dose-dependently increased from a basal level of 11.8 +/- 0.5 contra ctions per 5 min to 24.4 +/- 3.6 contractions per 5 min at pCGRP 10(-8) mol L-1. At this dose, the release of substance P and neurokinin A was signifi cantly increased to 470 +/- 149% and 217 +/- 26%, respectively, compared to basal release. The effect of pCGRP was unaffected by the addition of the n onpeptide antagonists for the NK-1 (CP-99994) and NK-2 receptors (SR48968), both at 10(-6) mol L-1, whereas atropine (10(-6) mol L-1) completely aboli shed the motor effect of pCGRP. The release of somatostatin was significant ly increased by 154 +/- 15% in response to CGRP at 10(-8) mol L-1. The rele ase of gastrin was unaffected by pCGRP, In conclusion, pCGRP increases cont ractile activity in the porcine antrum, an effect that involves cholinergic mechanisms but is independent of the release of substance P and neurokinin A. in addition, pCGRP increases the release of somatostatin but has no eff ect on gastrin release in the isolated perfused porcine antrum.