Hydrolysis of enkephalins in homogenates of anterior segment tissues of the albino rabbit eye.

The kinetics and pathways of hydrolysis of methionine enkephalin (TGGPM), leucine enkephalin (TGGPL), and [D-Ala2] met-enkephalinamide (TAGPM) in homogenates of anterior segment tissues of the albino rabbit eye were studied using reversed phase HPLC. Both TGGPM and TGGPL were equally susceptible to hydrolysis with a half-life ranging from 11-50 min and were 11-23 times more susceptible to hydrolysis than TAGPM. All three peptides were hydrolyzed most rapidly in the corneal epithelium, followed by the iris-ciliary body, conjunctiva, corneal stroma, lens, and tears. Aminopeptidases were responsible for over 90% of the hydrolysis of TGGPM and TGGPL, while dipeptidyl peptidase and dipeptidyl carboxylpeptidase were responsible for the remainder. In contrast, dipeptidyl carboxylpeptidase was principally responsible for the hydrolysis of TAGPM, which by design is resistant to aminopeptidase action. Overall, these findings suggest that, in order to deliver short chain peptides intraocularly from topical solution instillation, it will be necessary to control the ocular tissue activity of aminopeptidases principally and, to a lesser extent, the activity of dipeptidyl peptidase and dipeptidyl carboxylpeptidase.