Characterization of Bunazosin-Sensitive α1-Adrenoceptors in Human Renal Medulla

Abstract

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.

Tamsulosin Potently and Selectively Antagonizes Human Recombinant .ALPHA.1A/1D-Adrenoceptors: Slow Dissociation from the .ALPHA.1A-Adrenoceptor May Account for Selectivity for .ALPHA.1A-Adrenoceptor over .ALPHA.1B-Adrenoceptor Subtype

“…[10][11][12][13][14] Yamada et al 10,11) reported that the dissociation rate constant of [ 3 H]tamsulosin for α 1 -adrenoceptors was less than that of [ 3 H]prazosin in human prostate membrane from BPH patients. These results suggest that tamsulosin may dissociate slower than prazosin from human α 1A -adrenoceptors, the most abundant alpha-1 adrenoceptor subtype in human prostate tissue.…”

“…The binding kinetic studies of radiolabeled α 1 -adrenoceptor antagonist have been reported using α 1 -adrenoceptor membranes prepared from human or animal tissues. [10][11][12][13][14] …”