BINDING AND FUNCTIONAL-PROPERTIES OF DOXAZOSIN IN THE HUMAN PROSTATE ADENOMA AND CANINE BRAIN

The binding and functional properties of doxazosin were characterized in the canine brain and human prostate. 3H‐Doxazosin binding sites were characterized in canine brain and human prostate homogenates using saturation experiments. The binding of 3H‐doxazosin in the canine brain was consistently saturable and of high affinity. The mean equilibrium dissociation constant (Kd) and density (Bmax) of 3H‐doxazosin binding sites in the canine brain were 0.19 nM and 2.17 fmol/mg wet wt, respectively. The binding of 3H‐doxazosin in human prostate homogenates was not consistently linear owing to a relatively high proportion of nonspecific doxazosin binding sites. The mean Kd and Bmax of 3H‐doxazosin binding sites in the prostate determined from the saturation experiments yielding linear Scatchard plots were 0.2 nM and 0.51 fmol/mg wet wt. The pharmacology of doxazosin binding sites was further characterized in the canine brain using competitive binding experiments. The rank order of IC50corr values for norepinephrine, clonidine, yohimbine, terazosin, and prazosin indicated that doxazosin binds selectively to alpha1 and alpha2 adrenergic binding sites. The relative affinity of unlabeled doxazosin for alpha1 and alpha2 binding sites in the human prostate was determined by displacing 125I‐Heat or 3H‐rauwolscine with varying concentrations of unlabeled doxazosin. The affinity of doxazosin for alpha1 binding sites in the prostate adenoma was approximately 100‐fold greater than its affinity for alpha2 binding sites. The potency of doxazosin for inhibiting phenylephrineinduced contractions in the prostate indicated that prostate smooth muscle contraction is mediated by alpha1 adrenoceptors. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company