Chronotropic actions of cholecystokinin octapeptide on the rat heart

Cholecystokinin octapeptide (CCK-8) administered i.v. to urethane-anaesthetized rats or added to the perfusion stream of isolated rat hearts produced an immediate bradycardia. The size of this response was dose-related. Studies in vivo and in vitro using atropine and propranolol indicated that the response to CCK-8 was largely due to a direct action of the peptide on the heart. N-carbobenzoxy-tryptophan (CBZ-Trp), a cholecystokinin receptor antagonist, abolished the response of the isolated heart to CCK-8. Gastrin I did not produce bradycardia. The receptors on rat heart were similar to the classes of cholecystokinin receptors found in brain and exocrine pancreas in that CCK-8 rather than cholecystokinin tetrapeptide (CCK-4) was the preferred agonist.