暴露和对去甲肾上腺素的作用在多巴胺受体中介endothelium-independent放松分离的大鼠肠系膜小动脉。
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范德格拉夫PH值、Saxena公关Shankley NP,黑色JW
暴露和对去甲肾上腺素的作用在多巴胺受体中介endothelium-independent放松分离的大鼠肠系膜小动脉。
Br J杂志。1995年12月,116 (8):3237 - 42。
- PubMed ID
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8719802 (在PubMed]
- 文摘
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1。以前,我们报道,去甲肾上腺素(NA),除了α1-adrenoceptor-mediated收缩效应,可以使老鼠放松小肠系膜动脉(SMA)为了占陡峭席尔德情节得到化合物分为α1-adrenoceptor拮抗剂。在这项研究中,松弛剂NA的行动已经暴露大鼠隔离,endothelium-denuded SMA婚约的凝血恶烷A2-mimetic, U46619。2。NA,但选择性α2-adrenoceptor受体激动剂,UK14304,产生浓度收缩的SMA (pEC50 = 5.7 + / - 0.1)。precontraction后0.1 microM U46619 10 nM-30 microM NA产生进一步收缩(pEC50 = 6.1 + / - 0.2),而更高浓度的钠生产小,但意义重大,松弛剂反应。3所示。在1 microM哌唑嗪,0.1 -30 microM NA产生浓度依赖放松(pIC50 = 5.9 + / - 0.1)和0.1 microM precontraction后U46619。NA放松浓度效应曲线完全抑制由β1 /β1 microM 2-adrenoceptor拮抗剂,timolol。然而,当哌唑嗪的浓度增加了10倍(10 microM), NA再次产生浓度放松(pIC50 = 4.5 + / - 0.2)。 This relaxation concentration-effect curve was not blocked by a 10 fold higher concentration of timolol (10 microM), nor by the presence of idazoxan (10 microM), cyanopindolol (10 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), indomethacin (10 microM) or sulpiride (1 microM). However, haloperidol (10 microM) and (+/-)-SCH-23390 (10 nM) produced significant inhibition of the relaxation, suggesting the involvement of dopamine D1 receptors. 4. Dopamine also produced concentration-dependent relaxation following U46619 precontraction (pIC50 = 5.4 +/- 0.1) which was significantly inhibited by haloperidol and (+)-SCH-23390. Pretreatment with 10 microM phenoxybenzamine for 60 min produced a significant inhibition of the dopamine and NA relaxation curves and application of the operational model of agonism yielded estimates of the affinity (pKA = 5.3 +/- 0.2 and 4.4 +/- 0.2) and efficacy (log gamma = 0.06 +/- 0.11 and 0.01 +/- 0.10) for dopamine and NA, respectively, at D1 receptors. 5. HV723 (0.1 and 1 microM), a ligand that yielded a Schild plot slope parameter of unity as an antagonist of NA in the contractile assay, produced concentration-dependent inhibition of the NA-mediated relaxation (pA2 approximately 8). 6. The results of this study indicate that NA can activate D1 receptors mediating relaxation in the rat SMA at concentrations which were encountered in our previous receptor classification experiments using competitive alpha 1-adrenoceptor antagonists.