Characterization of prostatic alpha-l adrenoceptors in human benign prostatic hypertrophy.

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To identify and charaterize alpha-1 adrenoceptors in human prostates, specific binding of [^3H] prazosin and [^3H] bunazosin in crude prostatic membranes from patients with benign prostatic hypertrophy (BPH) was measured. Specific binding of [^3H] prazosin and [^3H] bunazosin was saturable, reversible and of high affinity (Kd values=0.35 nM and 1.03 nM, respectively), and it showed a pharmacological specificity as well as stereoselectivity which characterized alpha-1 adrenoceptors. Alpha-1 antagonists competed with both radioligands for the binding sites in human prostates in order : YM617 > prazosin > bunazosin > terazosin > naftopidil > urapidil. The potencies (pKi) of alpha-1 antagonists in competing for the radioligand binding sites in human prostates correlated well with their pharmacological potencies (pA_2) in the prostates. Scatchard analysis indicated that the decrease of prostatic [^3H] prazosin binding by prazosin, bunazosin and naftopidil was due to a significant in-crease … More in the Kd value without a change in the Bmax value. Also, the inhibitory effect of specific [^3H] prazosin binding by prazosin was identical in human prostate and aorta, but that by YM617 was approximately 14 times more potent in human prostate than in the aorta. Chlorethylclonidine treatment inhibited partially specific [^3H] prazosin binding in both tissues, thereby suggesting the coexistence of alpha-1 adrenoceptor subtypes (alpha-la and alpha-1b).There was a significant increase in the maximal number of binding sites for [^3H] prazosin and [^3H] bunazosin in hypertrophied prostates from BPH compared to normal tissues without BPH, whereas BPH had little effect on the dissociation constants for both radioligands. Also, there was a regional variation of alpha-1 adrenoceptor binding sites in the human prostate in order : inner zone > outer zone > prostatic urethra.Thus, we conclude : 1) [^3H] prazosin and [^3H] bunazosin selectively labels alpha-1 adrenoceptors in human prostates, 2) alpha-1 antagonists such as YM617 and prazosin antagonizes alpha-1 adrenoceptors (in a competitive and reversible manner) with high affinity, 3) YM617 is relatively selective antagonist of alpha-1 adrenoceptors in human prostate than in human aorta and 4) there is a greater density of alpha-1 adrenoceptor sites in BPH. Less