title: Interaction of cholecystokinin (CCK-33) and its C-terminal fragments: CCK-8 and CCK-4 with alpha- and beta-adrenoceptor agonists and antagonists in the cardiovascular system of rats. Part A.
abstract: The goal of the present study was to examine the interaction of cholecystokinin (CCK-33) and its fragments: C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4) with alpha- and beta-adrenoceptor agonists and antagonists. The effect of this interaction on arterial blood pressure and function of isolated heart was studied in rats. The results indicate that: 1) CCK-33 enhances the influence of catecholamines: noradrenaline and isoprenaline, mainly on the function of isolated heart. This peptide does not change cardiovascular effects of alpha-adrenoceptor antagonist--phentolamine. CCK-33 diminishes the influence of propranolol on the function of isolated heart. The hypotensive effect of beta-adrenoceptor antagonist is not affected by CCK-33. 2) CCK-8 does not alter cardiovascular effects of noradrenaline and isoprenaline. The peptide diminishes the hypotensive effect of phentolamine and reverses the hypotensive effect of propranolol. CCK-8 enhances the influence of propranolol and does not change the influence of phentolamine on the function of isolated heart. CCK-8 enhances bradycardia evoked by propranolol. 3) CCK-4 does not change the influence of noradrenaline and isoprenaline on arterial blood pressure and diminishes the hypotensive effect of phentolamine and propranolol. The peptide does not change cardiac effects of noradrenaline and diminishes the effects of isoprenaline, phentolamine and propranolol. On the basis of the present study, we concluded that CCK-33 and its fragments CCK-8 and CCK-4 modify the cardiovascular action of alpha- and beta-adrenoceptor agonists and antagonists. We suggest that effects we have observed correlate with the activation of the CCK-A receptors (CCK-33, CCK-8) or CCK-B receptors (CCK-4). CCK-related peptides may increase or reduce the effects of catecholamines indirectly through activation of alpha-adrenoceptors. We can not exclude direct action of the peptides on the heart.
authors.affiliation: Department of Pharmacology, Medical University, Białystok, Poland.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wiśniewska
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002766:Cholecystokinin / Q000494:pharmacology*; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology*; D013758:Tetragastrin / Q000494:pharmacology*
chemical_list: D018663:Adrenergic Agents; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D013758:Tetragastrin; D002766:Cholecystokinin; D011433:Propranolol; D007545:Isoproterenol; D012844:Sincalide; D009638:Norepinephrine; D010646:Phentolamine