Möller S, Edvinsson L, Adner M
Department of Internal Medicine, Lund University Hospital, Sweden.
Eur J Pharmacol. 1997 Jun 18;329(1):69-77. doi: 10.1016/s0014-2999(97)10106-6.
The aim of the present study was to investigate the level of regulation of the contractile endothelin ET(B) receptor which appears spontaneously after organ culture of vascular segments. Endothelin-1 elicited a strong contraction while the selective endothelin ET(B) receptor agonist, sarafotoxin 6c, had a negligible effect on fresh ring segments of rat mesenteric artery. After organ culture in serum-free Dulbecco's modified Eagle's medium at 37 degrees C (for 1 or 2 days) the endothelin-1-induced contraction was unchanged, whereas sarafotoxin 6c induced, after 1 day, a marked contraction which was further increased at day 2. The contraction induced by sarafotoxin 6c was significantly attenuated by the transcriptional inhibitor, actinomycin D, or the translational inhibitor, cyclohexamide, while the endothelin-1-induced contraction was much less affected. mRNA for endothelin ET(A) and endothelin ET(B) receptors was present in fresh human omental arteries denuded of endothelium. However, after organ culture, endothelin ET(B) mRNA was more prominent than endothelin ET(A) mRNA. Furthermore, the mRNA for both receptors was decreased after treatment with actinomycin D but not with cyclohexamide. This suggests that the endothelin ET(A) receptor is the dominating contractile receptor in fresh arteries while organ culture induces transcription and subsequent translation of contractile endothelin ET(B) receptors.
本研究的目的是调查血管段器官培养后自发出现的收缩性内皮素ET(B)受体的调节水平。内皮素-1引起强烈收缩，而选择性内皮素ET(B)受体激动剂沙拉毒素6c对大鼠肠系膜动脉新鲜环段的作用可忽略不计。在无血清的杜尔贝科改良伊格尔培养基中于37℃进行器官培养（1天或2天）后，内皮素-1诱导的收缩未改变，而沙拉毒素6c在培养1天后诱导出明显收缩，并在第2天进一步增强。沙拉毒素6c诱导的收缩被转录抑制剂放线菌素D或翻译抑制剂环己酰亚胺显著减弱，而内皮素-1诱导的收缩受影响较小。内皮素ET(A)和内皮素ET(B)受体的mRNA存在于去除内皮的新鲜人网膜动脉中。然而，器官培养后，内皮素ET(B) mRNA比内皮素ET(A) mRNA更显著。此外，用放线菌素D处理后两种受体的mRNA均减少，但用环己酰亚胺处理则未减少。这表明内皮素ET(A)受体是新鲜动脉中的主要收缩受体，而器官培养诱导了收缩性内皮素ET(B)受体的转录及随后的翻译。
