Vascular vasopressin receptors mediate inhibition of beta adrenergic receptor-induced cyclic AMP accumulation.
Beta adrenergic receptor agonists and forskolin stimulated cyclic AMP (cAMP) accumulation in cultured rat aortic smooth muscle cells (A-10). Furthermore, these cells display a high density of vasopressin receptors of the vascular (V1) subtype. Addition of vasopressin to these cells inhibited beta adrenergic agonist- and forskolin-stimulated cAMP accumulation by 30 to 40% and by 25 to 35%, respectively. The extent of inhibition was dependent on the concentration of vasopressin used. Half-maximal inhibition of cAMP accumulation by isoproterenol occurred at 8 X 10(-10) M vasopressin. Basal cAMP levels were not affected. The inhibition by arginine vasopressin was mediated by V1 receptors because the V2 renal receptor subtype selective agonists (1-deamino, 8-D-arginine)vasopressin and (1-deamino,4-valine,8-D-arginine)vasopressin were ineffective. Of the antagonists tested, the V1-selective antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine,8-arginine]vasopressin was more potent than the mixed V1/V2 antagonist [1-beta-mercapto--beta, beta-cyclopentamethylenepropionic acid), 2-D-(O-ethyl)tyrosine,4-valine 8-arginine]vasopressin. The V2-selective antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-D-isoleucine,4-valine,8-arginine]vasopressin displayed minimal ability to block the vasopressin-mediated inhibitory effect. These data demonstrate that in rat aortic smooth muscle cells V1 receptors are negatively coupled to adenylate cyclase. The studies presented suggest that the vasoconstrictor activity of vasopressin might involve inhibition of beta adrenergic receptor-mediated vascular relaxation through inhibition of cAMP accumulation.
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D017483:Receptors, Vasopressin
D011943:Receptors, Adrenergic, beta; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D005576:Colforsin; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol