Comparison of the alpha-adrenoceptor characteristics in human and canine prostate

Abstract

Alpha adrenoceptors, mediating contraction, have been shown to be present in strips of hypertrophic prostate surgically removed from patients with benign prostatic hypertrophy (BPH), providing a rational explanation for the demonstrated effectiveness of alpha antagonists in the symptomatic treatment of this disease. Inasmuch as the dog develops spontaneous and hormonally induced prostatic enlargement, studies were performed to compare the adrenoceptor characteristics of canine and human prostate to determine whether the dog represents a useful model to search for more effective alpha-adrenolytic therapy for human BPH. Norepinephrine produces contraction in isolated strips of canine prostate although it is only one-tenth as potent as previously reported in human tissue. In contrast, several selective alpha 1-adrenoceptor agonists are potent contractile agents in canine prostate, but are nearly inactive in the human tissue. This difference may be a consequence of their partial agonist character. The potency of selective alpha-adrenoceptor antagonists in blocking the norepinephrine-induced contractile response in both canine and human tissue is consistent with an action of norepinephrine on the alpha 1 adrenoceptor. The receptor dissociation constants for these antagonists are similar in prostatic tissue from dogs and humans, and the values in canine tissue correlate well with those obtained in the rabbit ear artery, a standard model for vascular alpha 1 adrenoceptors. Hence the dog may represent a useful model for studies of the potential responsiveness of human prostate to adrenergic agents.