Dibutyryl cyclic-AMP (DBcAMP) and theophylline partially inhibit the appearance of collagenase activity when added to cultures of ulcerating rabbit corneas. Drug treatment with DBcAMP also inhibits degradation of collagen in the explanted corneas as measured by hydroxyproline in the media. The hydrolysis product of DBcAMP, 5′-adenosine monophosphate (5′ AMP) is itself very effective in suppressing collagenase activity and the degradation of explant collagen. The mechanism(s) of the drug effects is not yet known but it is possible that the drugs affect the synthesis and/or the secretion of collagenase. The results suggest that "first messengers" exist which can prevent the secretion of corneal collagenase by raising endogenous cAMP in corneal cells through stimulation of the adenyl cyclase system. Eventual successful treatment of corneal ulceration might well require pharmacologic intervention at multiple levels: the biosynthesis, secretion, activation and activity of collagenase.
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience