Role of α₁-adrenoceptors and 5-HT₂ receptors in serotonin-induced contraction of rat prostate: autoradiographical and functional studies

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• 作者：Killam ; Anne L. ; Watts ; Stephanie W. ; Cohen ; Marlene L.
• 关键词：5-HT₂ receptor ; α ; -Adrenoceptor ; Prostate ; rat ; Smooth muscle ; Autoradiography
• 刊名：European Journal of Pharmacology
• 出版年：1995
• 出版时间：January 24, 1995
• 年：1995
• 卷：273
• 期：1-2
• 页码：7-14
• 全文大小：777 K

文摘

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 α₁ 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 α₁ receptors in the prostate. The concentration-response curve to 5-HT in the presence of 1 μM 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 [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 α₁-adrenoceptor ligand [¹²⁵I]HEAT ([β-(4-hydroxy-3-iodophenyl)ethyl-aminomethyl]-tetralone) confirmed the presence of α₁-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 α₁-adrenoceptors in the prostate. Thus activation of both α₁-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 α₁-adrenoceptors.