Wilkins P L, Suchovsky D, Berti-Mattera L N
Division of Hypertension, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Neurochem Res. 1997 Apr;22(4):409-18. doi: 10.1023/a:1027351525446.
Endothelins (ETs) are potent regulators of renal, cardiovascular and endocrine functions and act as neurotransmitters in the CNS. Here we report that immortalized Schwann cells express receptors for ETs and characterize some of the cellular events triggered by their activation. Specific binding of [125I]-ET-1 to Schwann cell membranes was inhibited by ET-1 and ETB-selective agonists ET-3, sarafotoxin 6c and [Ala1,3,11,15]-ET-1 with IC50cor values ranging between 2 and 20 nM. No competition was observed with the ETA receptor-selective antagonist BQ123. Incubation of [3H]-inositol pre-labeled Schwann cells with ET-1, ET-3 or sarafotoxin 6c elicited a concentration-dependent increase in the release of [P1 that reached a plateau at approximately 100 nM. The efficacy of [Ala1,3,11,15]-ET-1 (a linear peptide analog of ET-1) was half of that corresponding to ET-1. These stimulatory effects were partially blocked by pre-incubation with pertussis toxin. When Schwann cells were incubated in the presence of 100 nM ET-1 or ET-3 there was a significant inhibition of basal and isoproterenol-stimulated cAMP levels. The inhibitory effects of sarafotoxin 6c and [Ala1,3,11,15]-ET-1 on isoproterenol-stimulated cAMP levels were similar to that observed with ET-1. Pre-incubation with pertussis toxin completely prevented this effect. These observations indicate that immortalized Schwann cells express receptors for ET peptides (predominantly ETB) coupled to modulation of phospholipase C and adenylyl cyclase activities. The actions of ETs on Schwann cells provide a novel example of the influence of vascular factors on nerve function.
内皮素（ETs）是肾脏、心血管和内分泌功能的强效调节因子，在中枢神经系统中作为神经递质发挥作用。在此我们报告，永生化雪旺细胞表达ETs受体，并对其激活引发的一些细胞事件进行了表征。[125I]-ET-1与雪旺细胞膜的特异性结合受到ET-1和ETB选择性激动剂ET-3、蛙皮素6c和[Ala1,3,11,15]-ET-1的抑制，IC50cor值在2至20 nM之间。未观察到与ETA受体选择性拮抗剂BQ123的竞争。用ET-1、ET-3或蛙皮素6c孵育[3H]-肌醇预标记的雪旺细胞，会引起[P1释放的浓度依赖性增加，在约100 nM时达到平台期。[Ala1,3,11,15]-ET-1（ET-1的线性肽类似物）的效力是ET-1的一半。这些刺激作用被百日咳毒素预孵育部分阻断。当雪旺细胞在100 nM ET-1或ET-3存在下孵育时，基础和异丙肾上腺素刺激的cAMP水平受到显著抑制。蛙皮素6c和[Ala1,3,11,15]-ET-1对异丙肾上腺素刺激的cAMP水平的抑制作用与ET-1观察到的相似。百日咳毒素预孵育完全阻止了这种作用。这些观察结果表明，永生化雪旺细胞表达与磷脂酶C和腺苷酸环化酶活性调节相关的ET肽受体（主要是ETB）。ETs对雪旺细胞的作用为血管因子对神经功能的影响提供了一个新例子。
