Characterization of bunazosin-sensitive alpha1-adrenoceptors in human renal medulla.
We studied the characteristics of bunazosin-sensitive alpha1-adrenoceptors in human renal medullae by using renal-clearance studies and radioligand-binding assay. In 12 patients with hypertension, renal-clearance studies demonstrated that bunazosin significantly increased renal blood flow from 683 +/- 82 (SD) to 829 +/- 103 ml/min (p < 0.05) and decreased renal vascular resistance from 0.18 +/- 0.02 to 0.14 +/- 0.02 mm Hg/(ml/min) (p < 0.05), but that prazosin had little effect on renal function. In a radioligand-binding assay, specific, saturable, and stereoselective [3H]bunazosin binding, with a single class of binding sites (Kd = 2.7 +/- 1.4 nM; Bmax = 44 +/- 16 fmol/mg protein; n = 11) was detected in membrane preparations of human renal medullae. The rank order of potency of antagonists that inhibited [3H]bunazosin-binding was bunazosin (Ki in nM = 49) > prazosin (57) > yohimbine (3,900) > propranolol (29,000), and that of agonists, l-norepinephrine (7,400) > l-epinephrine (19,000) > d-norepinephrine (71,000). The competition curves fit a one-site model. These findings suggest that bunazosin-sensitive alpha1-adrenoceptors exist in human renal medullae and participate in the regulation of renal hemodynamics.
Yasuda
G
G
Second Department of Internal Medicine, Yokohama City University School of Medicine, Minami-ku, Japan.
Umemura
S
S
Ishii
M
M
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011224:Prazosin / Q000493:pharmacokinetics / Q000494:pharmacology; D011799:Quinazolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; C018176:bunazosin; D011224:Prazosin