Alpha1-adrenoceptor antagonist effect of (+/-)-dobutamine in rat isolated gastric artery preparation.
(+/-)-Dobutamine at concentrations < or =10(-5) M did not evoke contractions of rat gastric artery segments. However, when the tissues were contracted with methoxamine, (+/-)-dobutamine evoked concentration-dependent relaxation. The relaxant responses were not significantly affected by propranolol. In the same preparation, propranolol competitively antagonized isoprenaline-induced relaxation with a -log K(B) value of 7.90+/-0.26. (+/-)-Dobutamine did not relax arterial ring segments precontracted with vasopressin (10(-7) M). (+/-)-Dobutamine antagonized noradrenaline-induced contractions of the gastric artery segments. The pA2 value was 6.93+/-0.20, and the slope of the Schild regression line was 1.22+/-0.14. This value (slope) was not significantly different from 1, indicating competitive antagonism. Pretreatment of gastric artery segments with dobutamine before phenoxybenzamine (PBZ) protected against inactivation of alpha1-adrenoceptors by PBZ. The dose ratio of prazosin (3x10(-9) M) and (+/-)-dobutamine (10(-5) M) in combination was close to the expected sum of their individual dose ratios minus 1, indicating interaction with a common site. It was therefore concluded that (+/-)-dobutamine evoked relaxation of rat gastric artery segments by an action not involving beta-adrenoceptor activation but by blocking alpha1-adrenoceptors.
Oriowo
M A
MA
Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Safat. Oriowo@hsc.kuniv.edu.kw
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; D004280:Dobutamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013237:Stereoisomerism; D013270:Stomach / Q000098:blood supply*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D004280:Dobutamine; D011433:Propranolol; D008729:Methoxamine; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin