Mathison Y, Israel A
School of Medicine J. M. Vargas, Department of Biological Sciences, Universidad Central de Venezuela, Caracas.
Brain Res Bull. 1998;45(1):15-9. doi: 10.1016/s0361-9230(97)00274-8.
We investigated the effect of endothelins (ETs) on receptor-mediated cGMP formation in whole rat adrenal medulla. ET-3 increased cGMP formation in a concentration-dependent manner; in addition, all three isoforms of ETs, at equimolar doses, increased cGMP levels in similar degree. IRL-1620, a selective ET(B) receptor agonist, also increased cGMP formation, mimicking the effects of ETs, but the increase was higher than those produced by ETs. L-arginine analogue, N-nitro-L-arginine (L-NAME), and methylene blue and OQD, two inhibitors of soluble guanylyl cyclase, significantly inhibited the increase in cGMP production induced by ETs or IRL-1620. Likewise, the selective ET(B) receptor antagonist, BQ-788, significantly inhibited ET-1- or ET-3-induced cGMP generation. Our results demonstrate that in whole rat adrenal medulla, endothelins stimulate NO-induced cGMP generation through ET(B) receptors, and they support the concept that endothelins could play a role in the regulation of adrenal medulla function.
我们研究了内皮素（ETs）对大鼠肾上腺髓质中受体介导的环鸟苷酸（cGMP）生成的影响。ET-3以浓度依赖的方式增加cGMP的生成；此外，三种同工型的ETs在等摩尔剂量下，以相似程度增加cGMP水平。选择性ET(B)受体激动剂IRL-1620也增加cGMP的生成，模拟了ETs的作用，但增加幅度高于ETs所产生的。L-精氨酸类似物N-硝基-L-精氨酸（L-NAME）以及可溶性鸟苷酸环化酶的两种抑制剂亚甲蓝和OQD，显著抑制了ETs或IRL-1620诱导的cGMP生成增加。同样，选择性ET(B)受体拮抗剂BQ-788显著抑制ET-1或ET-3诱导的cGMP生成。我们的结果表明，在大鼠肾上腺髓质中，内皮素通过ET(B)受体刺激一氧化氮（NO）诱导的cGMP生成，并且支持内皮素可能在肾上腺髓质功能调节中发挥作用这一概念。
