CHARACTERIZATION OF THE RECEPTORS AND MECHANISMS INVOLVED IN THE CARDIOVASCULAR ACTIONS OF SCCK-8 IN THE PITHED RAT

1 The cardiovascular actions of cholecystokinin and related peptides w ere investigated in the pithed rat. The receptors and the mechanisms i nvolved in these experiments were characterized. 2 Sulphated cholecyst okinin octapeptide (sCCK-8, 0.1-100 nmol kg(-1) i.v.) elicited a dose- dependent bradycardia and increase in mean arterial blood pressure. Ne ither gastrin-17 nor pentagastrin had any effect at concentrations up to 100 nmol kg(-1). 3 Both the presser response and bradycardia elicit ed by sCCK-8 were reduced by the selective CCKA receptor antagonists, devazepide (0.5-50 nmol kg(-1)) and lorglumide (1-7 mu mol kg(-1)). Th e selective CCKB receptor antagonists, CI-988 (1 mu mol kg(-1)) and L- 365,260 (15 mu mol kg(-1)) did not inhibit the effects of sCCK-8. 4 Th e presser response induced with sCCK-8 was reduced by treatment with e ither phentolamine (3 mu mol kg(-1)) or guanethidine (2 mu mol kg(-1)) and was unaffected by treatment with propranolol, atropine or hexamet honium. The presser response also persisted following bilateral adrena lectomy. 5 The bradycardia induced with sCCK-8 was unaffected by treat ment with phentolamine, propranolol, guanethidine, atropine, hexametho nium or bilateral adrenalectomy, 6 The tetrapeptide of cholecystokinin (CCK-4) elicited a dose-dependent presser response but did not induce bradycardia. The presser response was unaffected by devazepide (50 nm ol kg(-1)), L-365260 (15 mu mol kg(-1)) or phentolamine (3 mu mol kg(- 1)). 7 In the pithed rat, sCCK-8 acted via CCKA receptors to increase arterial blood pressure indirectly, at least in part, through activati on of alpha-adrenoceptors. The observed bradycardia was also mediated by CCKA receptors but possibly through a direct action on the heart.