Dissociation of the spasmolytic and metabolic effects of glucagon

Glucagon and glucagon-(1-21)-peptide were equipotent with regard to inhibitory effect on the amplitude of electrically evoked contractions of the isolated guinea-pig ileum. The effect was not potentiated by isobutylmethylxanthine (IBMX) nor inhibited by phentolamine or propranolol. Both peptides inhibited intestinal motility in rabbits in vivo. Glucagon and equimolar doses of glucagon-(1-21)-peptide exerted a relaxing effect on the rabbit gall bladder in vitro and in vivo and increased bile flow in rats. Both peptides inhibited pentagastrin stimulated gastric acid secretion in cats. However, contrary to glucagon, glucagon-(1-21)-peptide did not increase blood glucose and plasma IRI levels after intravenous administration to rats in vivo. Whereas the entire glucagon molecule was required for the metabolic effects, the amino acid sequence (1-21) of glucagon exerted a full spasmolytic action on the enteric muscles and the biliary tree. The spasmolytic effects on these organs are therefore likely to be mediated via a mechanism that does not involve the activation of adenyl cyclase.