去甲肾上腺素在多巴胺受体介导的大鼠离体小肠系膜动脉内皮独立舒张作用的暴露和特征。
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Van der Graaf PH, Saxena PR, Shankley NP, Black JW
去甲肾上腺素在多巴胺受体介导的大鼠离体小肠系膜动脉内皮独立舒张作用的暴露和特征。
中国药物学杂志，1995 12月;116(8):3237-42。
- PubMed ID
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8719802 (PubMed视图］
- 摘要
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1.之前，我们报道了去甲肾上腺素(NA)，除了其α - 1肾上腺素受体介导的收缩作用外，还可能放松大鼠小肠系膜动脉(SMA)，以解释由α - 1肾上腺素受体拮抗剂类化合物获得的急剧席尔德图。在本研究中，NA的松弛作用已经暴露在大鼠分离，内皮剥脱SMA预收缩的血栓素a2模拟，U46619。2.NA，而不是选择性α 2-肾上腺素受体激动剂UK14304，产生浓度依赖性的SMA收缩(pEC50 = 5.7 +/- 0.1)。0.1微米U46619预收缩后，10微米-30微米NA产生进一步收缩(pEC50 = 6.1 +/- 0.2)，而较高浓度的NA产生较小但显著的松弛反应。3.0.1 microM U46619预收缩后，0.1-30 microM NA在1 microM吡唑嗪存在下产生浓度依赖性弛豫(pIC50 = 5.9 +/- 0.1)。钠弛豫浓度-效应曲线被1微米的β 1/ β 2肾上腺素受体拮抗剂替莫洛尔完全抑制。然而，当吡唑嗪浓度增加10倍(10微米)时，NA再次产生浓度依赖性弛豫(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.