Alpha-2 adrenoceptors in medullary thick ascending limbs of the rabbit kidney.
Marked differences in the characteristics of alpha-2 adrenoceptors in the kidney of various species have been reported. In addition, there are functional differences in alpha-2 adrenoceptors in various nephron segments of the same species. In this study we have characterized alpha-2 adrenoceptors in the medullary thick ascending limb (MTAL) isolated from the rabbit kidney. The equilibrium binding of [3H]rauwolscine to MTAL homogenates was measured after incubation for 45 min at 25 degrees C in the absence and presence of 10 microM phentolamine. The specific binding of [3H]rauwolscine was saturable with a Kd of 2.6 +/- 0.1 nM and maximal binding of 234 +/- 18 fmol/mg of protein. Adrenergic drugs competed with MTAL-bound [3H]rauwolscine with the following order of potency: 1) antagonists: rauwolscine = yohimbine > phentolamine >> prazosin = propranolol; and 2) agonists: oxymetazoline > clonidine > epinephrine > BHT 933 (azepexole) > alpha-methylnorepinephrine. Our results indicate that specific alpha-2 adrenoceptors are present in the rabbit MTAL. The high (> 1600) ratio of Ki of prazosin: oxymetazoline suggests that the alpha-2 adrenoceptors in the rabbit MTAL belong to an alpha-2A subtype. Guanabenz, iodoclonidine and epinephrine at high concentrations decreased forskolin- and vasopressin-stimulated cyclic AMP formation in the rabbit MTAL. These results suggest that alpha-2 adrenoceptors are negatively coupled to adenylate cyclase system in the MTAL.
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville.
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Mohuczy-Dominiak
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D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001667:Binding, Competitive; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000378:metabolism / Q000648:ultrastructure*; D007700:Kinetics; D008297:Male; D011817:Rabbits; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000378:metabolism; D013268:Stimulation, Chemical; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D001127:Arginine Vasopressin; D005576:Colforsin; D015016:Yohimbine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases