Effects of endothelin on cultured human and rat glomerular mesangial cells.
Figure 5 summarizes our results and the data in the literature with regard to both short-term signalling and long-term signalling induced by endothelin. Short-term signalling, which induces vasoconstriction, is undoubtedly mediated by multiple signals including increments of cytosolic calcium, stimulation of protein kinase C and alkalinization of the cytosol. Endothelin also activates negative feedback pathways including arachidonate release with the synthesis of vasorelaxant prostaglandins and potentiation, in a prostaglandin-dependent manner, of beta-adrenergic-stimulated adenylate cyclase. Long-term signalling is less well understood and may depend not only on phospholipase activation with subsequent changes of calcium and protein kinase C but also stimulation of other protein kinases which phosphorylate key intermediates. Endothelin stimulates the transient appearance of protooncogenes that might play a role in the induction of cellular proliferation.
Simonson
M
M
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Osanai
T
T
Wann
S
S
Baldi
E
E
Mené
P
P
Nakazato
Y
Y
Kester
M
M
Thomas
C
C
Dunn
M
M
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008934:Mitogens / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D010738:Type C Phospholipases / Q000032:analysis
D016232:Endothelins; D008934:Mitogens; D016718:Arachidonic Acid; D000242:Cyclic AMP; D010738:Type C Phospholipases; D002118:Calcium