Enhancement of apomorphine-induced penile erection in the rat by a selective α1D-adrenoceptor antagonist

被引:10
|
作者
Mizusawa, H
Hedlund, T
Sjunnesson, J
Brioni, JD
Sullivan, JP
Andersson, KE [1 ]
机构
[1] Univ Lund Hosp, Dept Clin Pharmacol, S-22185 Lund, Sweden
[2] Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA
关键词
intracavernous pressure; corpus cavernosum; cavernous artery; alpha(1)-subtype; electrical stimulation; nerves; prazosin;
D O I
10.1038/sj.bjp.0704773
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Effects of A-322312 (alpha(1B)-adrenoceptor (AR) antagonist), A-119637 (alpha(1)-AR antagonist), prazosin (non-selective alpha(1)-AR antagonist), and yohimbine (alpha(2)-AR antagonist) were studied in rat corpus cavernosum (CC) and cavernous artery (Ace) preparations. Effects of intracavernous (i.e.) or intraperitoneal (i.p.) administration of alpha(1)-AR antagonists on apomorphine-induced erections were investigated. 2 A-119637 attenuated electrically induced contractions in isolated CC (-logIC(50); 8.12 +/- 0.15), and relaxed noradrenaline (NA)-contracted preparations by more than 90% at 10(-7) m. At the same concentration, the -logEC(50) value for NA in Ace was altered from 6.79+/-0.07 to 4.86+/-0.13. In the CC and Ace, prazosin similarily inhibited contractile responses. 3 Inhibitory effects of A-322312 (10(-7) m) in electrically activated CC were 32.3+/-5.1%, whereas no effect on concentration-response curves for NA was observed in the Acc. Yohimbine (10(-8) m and 10(-7) m), enhanced electrically-induced contractions in isolated CC by 20 to 50%. At 10(-6) M, inhibitory effects of yohimbine were obtained. 4 A-119637 (0.3 mumol kg(-1), i.p.) tripled the number of erections, and produced a 6 fold increase in the duration of apomorphine-induced erectile responses. A-322312, prazosin, or yohimbine did not enhance erections induced by apomorphine. None of the alpha(1)-AR antagonists significantly increased ICP upon i.e. administration. Decreases in blood pressure were seen with A-119637 and prazosin. 5 The present findings show that there is a functional predominance of the alpha(1D)-AR subtype in the rat erectile tissue, and that blockade of this receptor facilitates rat penile erection induced by a suboptimal dose of apomorphine.
引用
收藏
页码:701 / 708
页数:8
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