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. 3 H‐Doxazosin binding sites were characterized in canine brain and human prostate homogenates using saturation experiments. The binding of 3 H‐doxazosin in the canine brain was consistently saturable and of high affinity. The mean equilibrium dissociation constant (K d ) and density (B max ) of 3 H‐doxazosin binding sites in the canine brain were 0.19 nM and 2.17 fmol/mg wet wt, respectively. The binding of 3 H‐doxazosin in human prostate homogenates was not consistently linear owing to a relatively high proportion of nonspecific doxazosin binding sites. The mean K d and B max of 3 H‐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 IC 50 corr values for norepinephrine, clonidine, yohimbine, terazosin, and prazosin indicated that doxazosin binds selectively to alpha 1 and alpha 2 adrenergic binding sites. The relative affinity of unlabeled doxazosin for alpha 1 and alpha 2 binding sites in the human prostate was determined by displacing 125 I‐Heat or 3 H‐rauwolscine with varying concentrations of unlabeled doxazosin. The affinity of doxazosin for alpha 1 binding sites in the prostate adenoma was approximately 100‐fold greater than its affinity for alpha 2 binding sites. The potency of doxazosin for inhibiting phenylephrineinduced contractions in the prostate indicated that prostate smooth muscle contraction is mediated by alpha 1 adrenoceptors.