Ohmura T, Sakamoto S, Hayashi H, Kigoshi S, Muramatsu I
Department of Pharmacology, Fukui Medical School, Japan.
Urol Res. 1993 May;21(3):211-5. doi: 10.1007/BF00590038.
The alpha 1-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [3H]prazosin bound to alpha 1-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [3H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct alpha 1-adrenoceptor subtypes was suggested: presumably subtypes alpha 1A (high affinity for prazosin and WB4101), alpha 1N (high affinity for only HV723) and alpha 1L (low affinity for the three antagonists) according to the recently proposed alpha 1-adrenoceptor subclassification. The density of subtype alpha 1L was much higher than that of subtypes alpha 1A and alpha 1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the alpha 1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through alpha 1L subtype alpha-adrenoceptors.
通过结合实验和功能实验对犬前列腺α1-肾上腺素能受体亚型进行了表征。在饱和实验中，[3H]哌唑嗪以高亲和力与α1-肾上腺素能受体结合。在置换实验中，未标记的哌唑嗪和WB4101对400 pM [3H]哌唑嗪的结合产生双相抑制，表明存在至少两个对哌唑嗪或WB4101具有不同亲和力的位点。高亲和力位点的比例约为10%。HV723也识别出两个不同的亲和力位点，但高亲和力位点的比例约为20%。根据这些结果，提示存在三种不同的α1-肾上腺素能受体亚型：根据最近提出的α1-肾上腺素能受体亚分类，推测为α1A亚型（对哌唑嗪和WB4101具有高亲和力）、α1N亚型（仅对HV723具有高亲和力）和α1L亚型（对三种拮抗剂具有低亲和力）。α1L亚型的密度远高于α1A和α1N亚型。在功能实验中，哌唑嗪、WB4101和HV723以低亲和力竞争性拮抗去甲肾上腺素的收缩反应，其亲和力接近α1L亚型的估计值。这些结果表明，犬前列腺中对去甲肾上腺素的收缩反应主要通过α1L亚型α-肾上腺素能受体介导。
