Sympathectomy reveals α1A- and α1D-adrenoceptor components to contractions to noradrenaline in rat vas deferens
Sympathectomy reveals α1A- and α1D-adrenoceptor components to contractions to noradrenaline in rat vas deferens
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DOI：
10.1038/sj.bjp.0705987
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发表时间：
2004-11-01
影响因子：
7.3
通讯作者：
Docherty, JR
中科院分区：
文献类型：
--
作者：
Cleary, L;Slattery, J;Docherty, JR
我们之前已经证明，大鼠输精管对外源性去甲肾上腺素的收缩主要涉及α (1A)-肾上腺素受体，但对内源性去甲肾上腺素的收缩主要涉及α (1D)-肾上腺素受体。在这项研究中，我们在放射配体结合和功能研究中研究了交感神经切除术对大鼠输精管α(1)-肾上腺素能受体亚型的影响在载体处理的组织中，[H-3]prazosin与α(1)-肾上腺素受体结合的拮抗剂位移与α(1)-肾上腺素受体的单一种群一致。一系列α(1)-肾上腺素能受体拮抗剂的结合亲和力以pK(i)值表示，并与α(1)-肾上腺素能受体亚型的已知亲和力相关。相关性仅与α (1A)-肾上腺素受体相关在6-羟基多巴胺（2 × 100 mg kg(-1) i.p）切除的大鼠交感神经组织中，对α (1D)-肾上腺素受体拮抗剂BMY 7378的结合亲和力与双位点模型最吻合在功能研究中，去甲肾上腺素在产生总（相位加强直）收缩而非强直收缩时的效力在交感神经切除大鼠的组织中增加根据BMY 7378和α (1A)-肾上腺素受体拮抗剂RS 100329.6的作用，交感神经切除大鼠的结果表明，相性收缩主要是α (1D)-肾上腺素受体介导的，而强直性收缩主要是α (1A)-肾上腺素受体介导的。由此得出结论，在配体结合和对外源性激动剂的收缩方面，载体处理大鼠输尿管中主要的α(1)-肾上腺素受体是α (1A)-肾上腺素受体。α (1D)-肾上腺素受体只能在化学交感神经切除术后通过配体结合检测到，但它参与去甲肾上腺素诱发的大鼠输精管收缩，特别是阶段性收缩。
1 We have previously demonstrated that contractions of rat vas deferens to exogenous noradrenaline involve predominantly alpha(1A)-adrenoceptors, but that contractions to endogenous noradrenaline involve predominantly alpha(1D)-adrenoceptors. In this study, we have examined the effects of sympathectomy on the subtypes of alpha(1)-adrenoceptor in rat vas deferens in radioligand binding and functional studies.2 In vehicle-treated tissues, antagonist displacement of [H-3]prazosin binding to alpha(1)-adrenoceptors was consistent with a single population of alpha(1)-adrenoceptors. Binding affinities for a range of alpha(1)-adrenoceptor antagonists were expressed as pK(i) values and correlated with known affinities for alpha(1)-adrenoceptor subtypes. The correlation was significant only with alpha(1A)-adrenoceptors.3 In tissues from rats sympathectomised with 6-hydroxy-dopamine (2 x 100 mg kg(-1) i.p.), binding affinity for the alpha(1D)-adrenoceptor antagonist BMY 7378 fitted best with a two-site model.4 In functional studies, the potency of noradrenaline at producing total (phasic plus tonic) but not tonic contractions was increased in tissues from sympathectomised rats.5 Results obtained from sympathectomised rats suggest that phasic contractions are mainly alpha(1D)-adrenoceptor mediated, whereas tonic contractions are mainly alpha(1A)-adrenoceptor mediated, based on the effects of BMY 7378 and the alpha(1A)-adrenoceptor antagonist RS 100329.6 It is concluded that the predominant alpha(1)-adrenoceptor in vehicle-treated rat vas deferens is the alpha(1A)-adrenoceptor, both in terms of ligand binding and contractions to exogenous agonists. The alpha(1D)-adrenoceptor is only detectable by ligand binding following chemical sympathectomy, but is involved in noradrenaline-evoked contractions, particularly phasic contractions, of rat vas deferens.