ROLE OF ALPHA(1)-ADRENOCEPTORS AND 5-HT(2) RECEPTORS IN SEROTONIN-INDUCED CONTRACTION OF RAT PROSTATE - AUTORADIOGRAPHICAL AND FUNCTIONAL-STUDIES

Urinary obstruction from benign prostatic hyperplasia is a common clinical problem possibly associated with excessive prostatic constriction around the urethra. These studies compared adrenergic and serotonergic functional activity to specific alpha(1) and serotonin (5-hydroxytryptamine; 5-HT) binding sites in the rat prostate. Isolated, left ventral lobes of the rat prostate were removed and examined for in vitro contraction. Norepinephrine-induced contraction of the rat prostate was competitively blocked by prazosin with an apparent antagonist dissociation constant (pK(B)) of 8.13. 5-HT also contracted the rat prostate. However, in the presence of prazosin, maximum 5-HT contraction was reduced by half suggesting that high concentrations of 5-HT can activate alpha(1) receptors in the prostate. The concentration-response curve to 5-HT in the presence of 1 mu M prazosin was competitively inhibited by the 5-HT2 receptor antagonist LY53857 (6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid 2-hydroxyl-1-methylpropylester (Z)-2-butenedioate (1:1)) (pK(B) = 9.02). Autoradiographic studies with [I-125]LSD (2-iodo-lysergic acid diethylamide) documented the presence of 5-HT, receptors since significant displacement of the radioligand occurred with 5-HT and LY53857, but not with prazosin. The alpha(1)-adrenoceptor ligand [I-125]HEAT ([beta-(4-hydroxy-3-iodophenyl)ethyl-aminomethyl]-tetralone) confirmed the presence of alpha(1)-adrenoceptors in the rat prostate since significant displacement of the radioligand occurred with prazosin, but not 5-HT or LY53857. The inability of prazosin to displace [I-125]LSD and the inability of 5-HT to displace [I-125]HEAT suggest that 5-HT cannot directly interact with alpha(1)-adrenoceptors in the prostate. Thus activation of both alpha(1)-adrenoceptors and 5-HT2 receptors resulted in contraction of the rat prostate, and 5-HT-induced contraction was mediated by activation of 5-HT2 receptors and the indirect activation of alpha(1)-adrenoceptors.