Stimulatory effect of thrombin on endothelin-1 production in isolated glomeruli and cultured mesangial cells of rats.
To determine whether endothelin-1 (ET-1) is released in close proximity to its binding sites on glomerular mesangial cells, and also to elucidate the regulatory factors responsible for its release, we measured immunoreactive ET-1 (ir-ET-1) in the incubation media of isolated glomeruli and cultured mesangial cells of rats using enzyme immunoassay under both basal and thrombin-stimulated conditions. ir-ET-1 was released time-dependently, from isolated glomeruli and cultured mesangial cells. Thrombin (2 U/ml) stimulated the release from both preparations. The release of immunoreactive big endothelin-1 (ir-big ET-1), which was assayed by using enzyme immunoassay, was also time-dependent, and the release was increased by thrombin (2 U/ml; at 4 h, 8 h, and 24 h) in cultured mesangial cells. The releases of big ET-1 and its converted product ET-1 from mesangial cells, an established target for ET-1, suggests that ET-1 acts as an autocrine factor for the cells.
Fukunaga
M
M
First Department of Medicine, Osaka University Medical School, Japan.
Fujiwara
Y
Y
Ochi
S
S
Yokoyama
K
K
Fujibayashi
M
M
Orita
Y
Y
Fukuhara
Y
Y
Ueda
N
N
Kamada
T
T
D000818:Animals; D001777:Blood Coagulation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013917:Thrombin / Q000494:pharmacology*
D016232:Endothelins; D012333:RNA, Messenger; D013917:Thrombin