Transcriptional regulated plasticity of vascular contractile endothelin ET(B) receptors after organ culture.
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.
Möller
S
S
Department of Internal Medicine, Lund University Hospital, Sweden.
Edvinsson
L
L
Adner
M
M
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014757:Viper Venoms / Q000494:pharmacology
D019332:Endothelin-1; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; D003609:Dactinomycin; D003513:Cycloheximide; D011188:Potassium; D009638:Norepinephrine