Testa R, Guarneri L, Ibba M, Strada G, Poggesi E, Taddei C, Simonazzi I, Leonardi A
Research Laboratories, Recordati S.p.A., Milan, Italy.
Eur J Pharmacol. 1993 Nov 16;249(3):307-15. doi: 10.1016/0014-2999(93)90527-o.
The alpha 1-adrenoceptor subtypes present in the smooth muscle of urethra and prostate of different animal species, including man, were characterized by using receptor binding techniques. In prostatic urethra and prostate membranes, [3H]prazosin labelled a single population of alpha 1-adrenoceptors (Hill coefficient not different from unity) with a high affinity in the range 0.21-0.51 nM. The number of specific [3H]prazosin binding sites was partially affected by chloroethylclonidine only in human and rat prostate membranes, whereas this agent proved practically devoid of activity in rabbit and dog prostate membranes as well as in the prostatic urethra membranes of all the animal species examined. These findings indicate that in prostatic and urethral membranes the alpha 1-adrenoceptors mainly belong to the alpha 1A subtype. The binding results were confirmed by in vitro functional studies on noradrenaline-induced contractions of rabbit and dog urethral preparations. The agonist-induced contractions were practically unaffected by preincubation of both tissues with chloroethylclonidine, but were sensitive to nifedipine. We found, moreover, a good correlation between the potency of different selective and non-selective alpha 1-adrenoceptor antagonists (WB-4101, 5-methylurapidil, phentolamine, spiperone, prazosin and urapidil) tested against the noradrenaline-induced contractions of rabbit urethra and their affinity for the alpha 1A-adrenoceptor subtype, no correlation with the affinity for the alpha 1B subtype, and a lower correlation with the affinity for the alpha 1C-adrenoceptor subtype.
利用受体结合技术对包括人类在内的不同动物物种尿道和前列腺平滑肌中的α1 - 肾上腺素能受体亚型进行了表征。在前列腺尿道和前列腺膜中，[3H]哌唑嗪标记了单一群体的α1 - 肾上腺素能受体（希尔系数与1无差异），亲和力较高，范围在0.21 - 0.51 nM。仅在人类和大鼠前列腺膜中，氯乙可乐定对特异性[3H]哌唑嗪结合位点的数量有部分影响，而在兔和犬的前列腺膜以及所有受试动物物种的前列腺尿道膜中，该药物几乎没有活性。这些发现表明，在前列腺和尿道膜中，α1 - 肾上腺素能受体主要属于α1A亚型。通过对兔和犬尿道制剂去甲肾上腺素诱导收缩的体外功能研究证实了结合结果。两种组织用氯乙可乐定预孵育后，激动剂诱导的收缩几乎不受影响，但对硝苯地平敏感。此外，我们发现，针对兔尿道去甲肾上腺素诱导收缩测试的不同选择性和非选择性α1 - 肾上腺素能拮抗剂（WB - 4101、5 - 甲基乌拉地尔、酚妥拉明、螺哌隆、哌唑嗪和乌拉地尔）的效力与其对α1A - 肾上腺素能受体亚型的亲和力之间具有良好的相关性，与对α1B亚型的亲和力无相关性，与对α1C - 肾上腺素能受体亚型的亲和力相关性较低。
