Endothelin-1 stimulates myristoylated alanine-rich C-kinase substrate (MARCKS) phosphorylation in rat cerebellar slices.

Protein phosphorylation induced by endothelins has been studied using [32P]orthophosphate-prelabelled rat cerebellar slices. Endothelin-1 increased phosphorylation of an 87 kDa protein in a time-dependent manner (reaching a maximum effect at about 2.5 min) and with an EC50 equal to 93 +/- 32 nM. Endothelin-3 and sarafotoxin 6c induced similar levels of phosphorylation. Endothelin-1 also promoted [3H]inositol phosphate accumulation with similar EC50 (71 +/- 7.5 nM). The phosphoprotein of 87 kDa seems to be myristoylated alanine-rich C-kinase substrate (MARCKS) as demonstrated by acetic acid extraction. In addition, 12-O-tetradecanoylphorbol-13-acetate (TPA) increased 87 kDa protein phosphorylation while Ro-31-8220, a specific protein kinase inhibitor, inhibited both TPA and endothelin-induced 87 kDa protein phosphorylation. Therefore, it is concluded that protein kinase C is involved in the endothelin action on cerebellum.