title: Characterization of the receptors and mechanisms involved in the cardiovascular actions of sCCK-8 in the pithed rat.
abstract: 1. The cardiovascular actions of cholecystokinin and related peptides were investigated in the pithed rat. The receptors and the mechanisms involved in these experiments were characterized. 2. Sulphated cholecystokinin octapeptide (sCCK-8, 0.1-100 nmol kg-1, i.v.) elicited a dose-dependent bradycardia and increase in mean arterial blood pressure. Neither gastrin-17 nor pentagastrin had any effect at concentrations up to 100 nmol kg-1. 3. Both the pressor response and bradycardia elicited by sCCK-8 were reduced by the selective CCKA receptor antagonists, devazepide (0.5-50 nmol kg-1) and lorglumide (1-7 mumol kg-1). The selective CCKB receptor antagonists, CI-988 (1 mumol kg-1) and L-365,260 (15 mumol kg-1) did not inhibit the effects of sCCK-8. 4. The pressor response induced with sCCK-8 was reduced by treatment with either phentolamine (3 mumol kg-1) or guanethidine (2 mumol kg-1) and was unaffected by treatment with propranolol, atropine or hexamethonium. The pressor response also persisted following bilateral adrenalectomy. 5. The bradycardia induced with sCCK-8 was unaffected by treatment with phentolamine, propranolol, guanethidine, atropine, hexamethonium or bilateral adrenalectomy. 6. The tetrapeptide of cholecystokinin (CCK-4) elicited a dose-dependent pressor response but did not induce bradycardia. The pressor response was unaffected by devazepide (50 nmol kg-1), L-365260 (15 mumol kg-1) or phentolamine (3 mumol kg-1). 7. In the pithed rat, sCCK-8 acted via CCKA receptors to increase arterial blood pressure indirectly, at least in part, through activation of alpha-adrenoceptors. The observed bradycardia was also mediated byCCKA receptors but possibly through a direct action on the heart.
authors.affiliation: Peptic Ulceration Group, Pharmacology I, Glaxo Research and Development Ltd, Ware, Herts.
authors.forename: A J
authors.initials: AJ
authors.lastname: Gaw
authors.forename: D M
authors.initials: DM
authors.lastname: Hills
authors.forename: C F
authors.initials: CF
authors.lastname: Spraggs
mesh_terms: D000315:Adrenalectomy; D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced; D002766:Cholecystokinin / Q000633:toxicity*; D003655:Decerebrate State; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000008:administration & dosage / Q000633:toxicity; D006145:Guanethidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006728:Hormones / Q000008:administration & dosage / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D012844:Sincalide / Q000633:toxicity*; D013758:Tetragastrin / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D018663:Adrenergic Agents; D001570:Benzodiazepinones; D005755:Gastrins; D006727:Hormone Antagonists; D006728:Hormones; D007211:Indoles; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C065599:PD 134308; C013550:gastrin 17; D008536:Meglumine; D002766:Cholecystokinin; D010418:Pentagastrin; D011377:Proglumide; D020109:Devazepide; C048181:lorglumide; D012844:Sincalide; D010646:Phentolamine; D006145:Guanethidine