Prostatic specimens of adenomatous tissue (PA) were obtained from the lateral lobe of the prostate in patients with benign prostatic hyperplasia (BPH). Non-hyperplastic specimens of the outer prostatic tissue (PC) were taken from the dorsal part of the prostate in patients undergoing cystourethrectomy. Effects of alpha-adrenoceptor and muscarinic receptor active drugs were studied. Noradrenaline (NA) and the alpha 1-adrenoceptor agonist phenylephrine induced concentration-dependent contractions in PC and PA preparations. The alpha 2-adrenoceptor agonist clonidine was without effect on PC but contracted PA preparations; it was less potent and had less intrinsic activity than phenylephrine. In PC and PA strips, the alpha 1-adrenoceptor antagonist prazosin was more effective than the alpha 2-adrenoceptor antagonist rauwolscine to inhibit NA-induced contractions. Prazosin, but not rauwolscine, inhibited electrically induced contractions in PC strips. The muscarinic receptor agonists acetylcholine and carbachol were without effect in PC and PA preparations. In both PC and PA preparations, clonidine decreased and rauwolscine increased the electrically elicited 3H-efflux after pre-loading of the tissues with 3H-noradrenaline. Carbachol and scopolamine were without consistent effects. In radioligand receptor binding experiments, the occurrence of alpha 1- and alpha 2-adrenoceptor binding sites was demonstrated; the ratio between alpha 1- and alpha 2-adrenoceptor binding sites was 3/2 in PC, but 2/3 in PA tissue. By autoradiography, muscarinic receptors were found to be localized exclusively to the glandular epithelium, consistent with the lack of contractile effects of muscarinic receptor active drugs on PC and PA preparations. Our results thus suggest that the main alpha-adrenoceptor function in human prostatic smooth muscle is of the alpha 1-type and that muscarinic receptors in the prostate are involved in processes other than control of smooth muscle contraction.
Prazosin, a selective alpha-1-adrenoceptor blocker, was used in a double-blind crossover study in 20 men with benign prostatic obstruction. Maximum and average flow rates increased, and residual volume and obstructive symptoms were reduced. Voiding pressure parameters, bladder capacity and irritative symptoms did not change significantly. No side effects were noted. We conclude that prazosin seems to be an effective therapeutic alternative in patients with benign prostatic obstruction.
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