SENSITIZATION BY CALYCULIN-A OF BRAIN CAPILLARY ENDOTHELIAL-CELLS TO ENDOTHELIN-1

1 Cultured brain capillary endothelial cells of the rat respond to end othelin-1 (ET-1) by an increased activity of the Na+, K+, 2Cl(-), cotr ansporter and a mobilization of intracellular Ca2+ stores. 2 Calyculin A (1-30 nM), but not okadaic acid, sensitizes up to 100 fold the Na+, K+, 2Cl(-) cotransporter to the action of ET-1. 3 Calyculin A (30 nM) does not modify the binding properties of ET-1 to ET(A) receptors. 4 Calyculin A (30 nM) inhibits ET-1 induced intracellular Ca2+ mobilizat ion. 5 It is concluded that inhibition of protein phosphatase 1 select ively modifies the repertoire of intracellular actions of ET-1 and fav ours actions that are unrelated to the phospholipase C signalling casc ade.