alpha(1)-adrenoceptor subtypes and effect of alpha(1A)-adrenoceptor agonist NS-49 on guinea pig nasal mucosa vasculature.
alpha(1)-adrenoceptor subtypes and effect of alpha(1A)-adrenoceptor agonist NS-49 on guinea pig nasal mucosa vasculature.
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α(1)-肾上腺素受体亚型以及 α(1A)-肾上腺素受体激动剂 NS-49 对豚鼠鼻粘膜脉管系统的影响。
DOI：
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发表时间：
2000
影响因子：
5
通讯作者：
H. Tsuru
中科院分区：
文献类型：
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作者：
N. Tanimitsu;K. Yajin;M. Sasa;H. Tsuru
现在已经很清楚，α(1)-肾上腺素能受体组成一个不同的家族。在本研究中，我们研究了豚鼠鼻粘膜血管中的α(1)-肾上腺素能受体亚型。将一条长方形的豚鼠鼻粘膜悬浮在含有Krebs‘s碳酸氢盐溶液的器官浴中。张力的变化是等距记录的。以累积的方式获得激动剂的浓度-反应曲线。去甲肾上腺素对鼻黏膜血管的收缩作用最大。NS-49、盐酸磺胺(((R)-(-)-3‘-(2-amino-1-hydroxyethyl)-4’-fluoromethane)和羟甲唑啉为部分激动剂。NS-49和羟甲唑啉的内源活性分别为0.50+/-0.22和0.29+/-0.17，而去甲肾上腺素为1.00。哌唑嗪和可能的α(1A)受体拮抗剂WB-4101(2-(2，6-dimethoxyphenoxyethyl)aminomethyl-1，4-benzodioxane)和5-甲基乌拉地尔竞争性地拮抗去甲肾上腺素的反应(Pa2)。相反，α(1B)和α(1D)肾上腺素受体拮抗剂(螺环酮和BMY7378(8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4，5]-7，9-二酮)不具有竞争性拮抗作用。这些结果表明，豚鼠鼻粘膜血管以α(1A)-亚型为主，α(1L)(或α(1N))亚型也可能存在。此外，NS-49可能被证明是一种鼻粘膜血管收缩药，可以改善鼻塞。
It is now clear that alpha(1)-adrenoceptors comprise a heterogeneous family. In the present study, we characterized the alpha(1)-adrenoceptor subtype in the nasal mucosa vasculature of guinea pigs. A rectangular strip of guinea pig nasal mucosa was suspended in an organ bath containing Krebs' bicarbonate solution. Changes in tension were recorded isometrically. Concentration-response curves for agonists were obtained in a cumulative manner. Noradrenaline produced the greatest contraction of the nasal mucosa vasculature. NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane sulfonanilide hydrochloride) and oxymetazoline worked as partial agonists. The intrinsic activities of NS-49 and oxymetazoline were 0.50+/-0.22 and 0.29+/-0.17, respectively, compared with noradrenaline (=1.00). Prazosin and the putative alpha(1A)-adrenoceptor antagonists WB-4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane) and 5-methylurapidil antagonized the response to noradrenaline competitively (pA(2) for prazosin<9.0). Conversely, putative alpha(1B) and alpha(1D)-adrenoceptor antagonists (spiperone and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4, 5]decane-7,9-dione), respectively) did not antagonize competitively. These results suggest that the alpha(1A)-subtype is predominant and that the alpha(1L) (or alpha(1N)) subtype may also be present in the guinea pig nasal mucosa vasculature. Furthermore, NS-49 might prove to be a nasal mucosa vasoconstrictor, which will improve nasal obstruction.