人输精管α 1l -肾上腺素能受体亚型的功能和放射配体结合特性

B. J. Davis, M. Wiener, C. R. Chapple, D. J. Sellers, R. Chess-Williams
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引用次数: 5

摘要

α -肾上腺素受体拮抗剂可引起射精功能障碍。人输精管的收缩是通过α 1a -肾上腺素受体介导的,本研究探讨了α 1l -肾上腺素受体的低亲和力状态是否参与了输精管收缩的介导。在功能实验和[3H]坦索罗辛结合实验中,测定了受体亚型选择性拮抗剂的效价和受体亚型选择性拮抗剂的亲和力,以鉴定人输精管中存在的α1-肾上腺素能受体亚型群体。α α -肾上腺素受体选择性激动剂A61603是一种完全激动剂,比去甲肾上腺素强250倍。哌唑嗪对苯肾上腺素的收缩反应具有低亲和力(pKd = 8.6)。只有高浓度的RS17053对苯肾上腺素产生拮抗反应,并且产生相对较低的亲和力估计为7.0。BMY7378 (α 1d -肾上腺素受体选择性)具有低亲和力(pKd = 6.7),而坦索罗新(α1A-和α 1d -肾上腺素受体选择性)具有高亲和力(pKd = 9.9)。[3H]坦索罗辛以高亲和力与人输精管膜结合(pKd = 10.0)。Prazosin、RS17053和BMY7378与[3H]tamsulosin在单个群体结合位点上的亲和力较低(pKd值分别为8.5、7.2和6.3)。这些功能和放射配体结合数据表明,人类输精管具有均匀的α1-肾上腺素受体,这些α1-肾上腺素受体具有假定的α 1l -肾上腺素受体的药理特性,与先前在人类前列腺中发现的功能受体相同。
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Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens

  1. Alpha1-adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A-adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L-adrenoceptor) is involved in mediating contractions of this tissue.
  2. The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [3H]tamsulosin binding experiments to identify the α1-adrenoceptor subtype population present in the human vas deferens.
  3. The α1A-adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D-adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A- and α1D-adrenoceptor selective) had a high affinity (pKd = 9.9).
  4. [3H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [3H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively).
  5. These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1-adrenoceptors which have the pharmacological properties of the putative α1L-adrenoceptor, the same functional receptor previously identified in the human prostate.
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Issue Information Autonomic and Autacoid Pharmacology: Goodbye and thank you Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue Retraction: Dopamine receptor immunohistochemistry in the rat choroid plexus. Issue Information
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