Role of alpha 1-adrenoceptors and 5-HT2 receptors in serotonin-induced contraction of rat prostate: autoradiographical and functional studies

• Published in: European journal of pharmacology 1995-01, Vol.273 (1-2), p.7-14
• Main Authors: Killam, A L, Watts, S W, Cohen, M L
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Autoradiography; Binding, Competitive - drug effects; In Vitro Techniques; Iodine Radioisotopes; Lysergic Acid Diethylamide; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Norepinephrine - antagonists & inhibitors; Norepinephrine - pharmacology; Phenethylamines; Prostate - drug effects; Rats; Rats, Inbred WKY; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Serotonin - drug effects; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Tetralones
• ISSN: 0014-2999

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 (pKB) 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 microM 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)) (pKB = 9.02). Autoradiographic studies with [125I]LSD (2-iodo-lysergic acid diethylamide) documented the presence of 5-HT2 receptors since significant displacement of the radioligand occurred with 5-HT and LY53857, but not with prazosin. The alpha 1-adrenoceptor ligand [125I]HEAT ([beta-(4-hydroxy-3-iodophenyl)ethylaminomethyl]-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 [125I]LSD and the inability of 5-HT to displace [125I]HEAT suggest that 5-HT cannot directly interact with alpha 1-adrenoceptors in the prostate.