Alpha 1-adrenoceptors in human prostate: characterization and binding characteristics of alpha 1-antagonists

The role of alpha 1-adrenoceptors in the mediation of autonomic functions, particularly in the control of the cardiovascular system, is widely known. It has been shown that alpha 1-adrenoceptors localized in human prostate mediate the contraction of prostatic smooth muscles which produces an increase in the intraurethral pressure and thus, these receptors are important in the regulation of bladder outlet resistance. Alpha 1-antagonists such as prazosin relieve the symptoms of bladder outlet obstruction in men with symptomatic benign prostatic hypertrophy (BPH) by blocking alpha 1-adrenoceptors, thereby decreasing prostatic tone and urethral resistance. Thus, alpha 1-adrenergic stimulation may be one of the most important factors in the development of urinary obstruction in BPH. Alpha 1-adrenoceptors in human prostate have been identified and characterized extensively by functional, radioligand binding and molecular biological techniques. These studies provide evidence in support of the concept that the alpha 1C-subtype forms the majority of alpha 1-adrenoceptors in human prostatic smooth muscles. It has been shown that YM617 (tamsulosin) and naftopidil have higher affinities to alpha 1-adrenoceptors in the prostate than in the aorta. Some alpha 1-antagonists, such as prazosin and terazosin, are not selective with respect to alpha 1-adrenoceptor subtypes, while others, such as 5-methylurapidil and indoramin, show higher potencies for alpha 1C-adrenoceptors and much lower potencies for alpha 1A- and alpha 1B-subtypes. In conclusion, the recent findings from pharmacological and molecular biological studies indicate that selective antagonists of alpha 1C-adrenoceptors could be effective in the treatment of urinary obstruction in symptomatic BPH with fewer cardiovascular side effects.