Inhibition of adenylate cyclase activity in the corneal epithelium by anti-inflammatory steroids

Adenylate cyclase activity in bovine corneal epithelial or rat kidney particulate fractions was completely inhibited by clinically employed levels of anti-inflammatory steroids. Dose-response studies using several steroids showed that dexamethasone phosphate was the most potent enzyme inhibitor, followed respectively by prednisolone phosphate and hydrocortisone phosphate. Enzyme inhibition occurred regardless of the level or mechanism of adenylate cyclase activation, although agonist-stimulated activity was more sensitive to inhibition than fluoride-stimulated activity. Steroids appear to cause a direct, reversible and non-competitive inhibition of adenylate cyclase, affecting both the apparent substrate affinity and maximum velocity of the enzyme. Application of high levels of anti-inflammatory steroids may block the reported cyclic AMP-mediated effects of increased epithelial wound closure rates and stimulated epithelial basement membrane protein synthesis in a healing cornea.