Pharmacological characterization of alpha 1-adrenoceptor subtypes in the human prostate: functional and binding studies.
Pharmacological characterization of alpha 1-adrenoceptor subtypes in the human prostate: functional and binding studies.
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DOI：
10.1111/j.1464-410x.1994.tb09186.x
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发表时间：
1994-11
期刊：
影响因子：
--
通讯作者：
I. Muramatsu;M. Oshita;T. Ohmurs;S. Kigoshi;Hironobu Akino;M. Gobara;K. Olada
中科院分区：
文献类型：
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作者：
I. Muramatsu;M. Oshita;T. Ohmurs;S. Kigoshi;Hironobu Akino;M. Gobara;K. Olada
目的应用功能和结合研究方法鉴定人良性前列腺肥大组织中α 1肾上腺素受体亚型。材料与方法本研究采用9例良性前列腺肥大患者行开放性前列腺切除术的前列腺组织条。结果5例前列腺条对去甲肾上腺素和苯肾上腺素产生明显的收缩反应，而对可乐定无反应。去甲肾上腺素诱导的收缩反应被代表性α 1-肾上腺素受体拮抗剂（哌唑嗪、WB 4101、5-甲基乌拉地尔和HV 723）竞争性拮抗，解离常数（pKB）< 8.5。氯乙基可乐定预处理对去甲肾上腺素的收缩反应没有影响。在5个前列腺的饱和实验中，[3 H]-哌唑嗪以两种不同的亲和力结合到前列腺膜上（pKD分别为9.95 +/- 0.07和8.71 +/- 0.04，Bmax分别为151 +/- 8和138 +/- 3 fmol/mg蛋白）。未标记的哌唑嗪和WB 4101双相取代200 pM [3 H]-哌唑嗪的结合;每种拮抗剂的高和低pKI值与饱和实验中[3 H]-哌唑嗪的两个pKD值一致。5-甲基乌拉地尔和HV 723取代了[3 H]-哌唑嗪的单相结合，亲和力（pKI）接近8.5。结论：这些结果表明，在人前列腺中存在至少两种不同的α 1肾上腺素受体亚型（可能是对哌唑嗪和WB 4101具有高亲和力的α 1C亚型，以及对拮抗剂具有低亲和力的假定α 1 L亚型），其中后一种亚型可能主要参与对去甲肾上腺素的收缩反应。
OBJECTIVE To characterize the alpha 1-adrenoceptor subtypes of the human benignly enlarged prostate using functional and binding studies. MATERIALS AND METHODS Strips of prostatic tissue taken from nine patients with benign prostatic hypertrophy who were undergoing open prostatectomy were used in the study. RESULTS The strips isolated from five prostates produced a large contraction in response to noradrenaline and phenylephrine but not to clonidine. The contractile response induced by noradrenaline was competitively antagonized by representative alpha 1-adrenoceptor antagonists (prazosin, WB4101, 5-methylurapidil and HV723), the dissociation constants (pKB) being < 8.5. Pre-treatment with chloroethylclonidine was without effect on the contractile response to noradrenaline. In saturation experiments with five prostates, [3H]-prazosin bound to the prostate membranes with two distinct affinities (pKD = 9.95 +/- 0.07 and 8.71 +/- 0.04, Bmax = 151 +/- 8 and 138 +/- 3 fmol/mg protein, respectively). Unlabelled prazosin and WB4101 biphasically displaced the binding of 200 pM [3H]-prazosin; the resulting high and low pKI values for each of the antagonists were consistent with the two pKD values obtained for [3H]-prazosin in the saturation experiments. 5-Methylurapidil and HV723 displaced the [3H]-prazosin binding monophasically with an affinity (pKI) close to 8.5. CONCLUSIONS These results suggest the presence of at least two distinct alpha 1-adrenoceptor subtypes (presumably an alpha 1C subtype with a high affinity for prazosin and WB4101, and a putative alpha 1L subtype with a low affinity for the antagonists) in the human prostate, in which the latter subtype may be predominantly involved in the contractile response to noradrenaline.