Involvement of the microtubular system in the endothelin-1 secretion from porcine aortic endothelial cells.
The effects of certain microtubule-disrupting agents on endothelin-1 (ET-1) secretion from porcine aortic endothelial cells were studied. When endothelial cells were treated with thrombin (1 unit/mL), a significant increase in ET-1 secretion was detected in the incubation medium, while ET-1 secretion in the medium was diminished when the cells were treated simultaneously with either colchicine or vinblastine (10(-8)-10(-6) M). In such cases, however, the ET-1 content detected in the cells increased dose-dependently in accordance with the concentrations of the microtubule-disrupting agents. The intracellular accumulation of ET-1 was observed both in mitochondrial and microsomal fractions. On the other hand, thrombin produced a significant increase in polymerized tubulin content without affecting the total tubulin content. A thrombin-induced increase in the intracellular Ca2+ concentration of endothelial cells was inhibited by treatment with either colchicine or vinblastine. These results seem to indicate that the microtubular system may play an important role in ET-1 secretion from endothelial cells.
Kitazumi
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Mio
M
M
Tasaka
K
K
D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008162:Lumicolchicines / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism*; D011863:Radioimmunoassay; D012270:Ribosomes / Q000378:metabolism; D013552:Swine; D013917:Thrombin / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology
D016232:Endothelins; D008162:Lumicolchicines; D014404:Tubulin; C042109:lumicolchicine; D014747:Vinblastine; D013917:Thrombin; D002118:Calcium