Role of alpha sub(1)-adrenoceptors and 5-HT sub(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 sub(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 sub(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 sub(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-HT sub(2) receptor antagonist LY53857 (6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid 2-hydroxyl-1-methylpropylester (Z)-2-butenedioate (1:1)) (pK sub(B) = 9.02). Autoradiographic studies with [ super(125)I]LSD (2-iodo-lysergic acid diethylamide) documented the presence of 5-HT sub(2) receptors since significant displacement of the radioligand occurred with 5-HT and LY53857, but not with prazosin. The alpha sub(1)-adrenoceptor ligand [ super(125)I]HEAT ([ beta -(4-hydroxy-3-iodophenyl) ethylaminomethyl]-tetralone) confirmed the presence of alpha sub(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 [ super(125)I]LSD and the inability of 5-HT to displace [ super(125)I]HEAT suggest that 5-HT cannot directly interact with alpha sub(1)-adrenoceptors in the prostate. Thus activation of both alpha sub(1)-adrenoceptors and 5-HT sub(2) receptors resulted in contraction of the rat prostate, and 5-HT-induced contraction was mediated by activation of 5-HT sub(2) receptors and the indirect activation of alpha sub(1)-adrenoceptors.