Endothelins inhibit adenylate cyclase in brain capillary endothelial cells.
The action of endothelins (Et) on cAMP formation was studied in endothelial cells from rat brain microvessels. Et-1 and Et-3 had no action by themselves. They both inhibited cholera toxin stimulated adenylate cyclase by about 50%. K0.5 values were observed at 2 nM and 40 nM for Et-1 and Et-3 respectively, indicating an involvement of a low affinity Et-3 receptor. Coupling to adenylate cyclase was achieved by a pertussis toxin sensitive mechanism. Another action of endothelins in brain capillary endothelial cells was to stimulate phospholipase C. This action involved a low affinity Et-3 receptor and a pertussis toxin insensitive mechanism. It is concluded that in brain capillary endothelial cells, ETA like receptors are coupled to phospholipase C and to adenylate cyclase via two different mechanisms.
Ladoux
A
A
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Valbonne, France.
Frelin
C
C
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D002999:Clone Cells; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D007295:Inositol Phosphates / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D017466:Receptors, Endothelin; D010738:Type C Phospholipases / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D016232:Endothelins; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D002772:Cholera Toxin; D010738:Type C Phospholipases