Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells.
To elucidate the cellular mechanism by which endothelin (ET) is secreted, we have studied the effects of a variety of vasoactive agents on the secretion of immunoreactive (IR)-ET from cultured bovine endothelial cells (EC). Confluent bovine EC cultured in serum-free medium secreted IR-ET as a function of time. Not only thrombin, but also vasoconstrictive hormones, such as arginine-vasopressin (AVP) and angiotensin (ANG) II, dose-dependently stimulated IR-ET secretion, and these effects were completely abolished by V1-receptor antagonist and [Sar1,Ala8]-ANG II, respectively. Protein kinase C (PKC)-activating phorbol ester and Ca2+ ionophore ionomycin had stimulatory effects on IR-ET secretion, and the combination of both compounds had a synergistic effect. These data suggest that AVP and ANG II, like thrombin, stimulate ET secretion from EC by a mechanism possibly involving receptor-mediated mobilization of intracellular Ca2+ and activation of PKC.
Emori
T
T
Second Department of Medicine, Tokyo Medical and Dental University, Japan.
Hirata
Y
Y
Ohta
K
K
Shichiri
M
M
Marumo
F
F
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D002339:Carotid Arteries; D002417:Cattle; D002478:Cells, Cultured; D004357:Drug Synergism; D016232:Endothelins; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology; D015759:Ionomycin; D007700:Kinetics; D010455:Peptides / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012504:Saralasin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D016232:Endothelins; D004987:Ethers; D010455:Peptides; D000804:Angiotensin II; D001127:Arginine Vasopressin; D015759:Ionomycin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D011493:Protein Kinase C; D013917:Thrombin; D012504:Saralasin; D013755:Tetradecanoylphorbol Acetate