Participation of both ‘enkephalinase’ and aminopeptidase activities in the metabolism of endogenous enkephalins

Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia.

“…When (21), including modification of monoamine turnover (42)(43)(44), and might trigger control mechanisms regulating enkephalin release (8,9). YGG does not arise from YGGFM selectively, since both the substrate specificity of enkephalinase (30)(31)(32)(33) and release experiments from brain slices (52) for about half the total YGGFM degradation (15). Hence, the fairly close agreement between the present estimates of the YGG turnover and YGGFM accumulation rates might to a certain extent be fortuitous.…”

“…This approach obviously requires a knowledge of the metabolic pathways of endogenous OPs. Endogenous enkephalins [Tyr-Gly-Gly-Phe-Met (YGGFM) and Tyr-GlyGly-Phe-Leu (YGGFL)] are degraded through (i) cleavage of the Tyr-Gly bond at residues 1 and 2 by a bestatin-sensitive aminopeptidase activity (14,15) (15,25) or in vivo (26,27), and its degradation is prevented by bestatin (15).…”

Leupeptin, a thiol proteinase inhibitor, causes a selective impairment of spatial maze performance in rats

“…Moreover, the latency to escape from a mild footshock in naive animals (i.e., on the first trial of conditioning) treated with high concentrations of the drug were comparable to those found in controls. In contrast, inhibitors of amino peptidases and enkephalinases are reported to cause a marked increase in escape latency (de la Baume et al, 1983). Certain forms of learning also remain intact in the presence of leupeptin.…”

A serine peptidase responsible for the inactivation of endogenous cholecystokinin in brain.

“…However, numerous peptidases capable of hydrolyzing neuropeptides are present in cerebral membranes, and metabolic pathways of exogenous neuropeptides may not reliably reflect those responsible for endogenous neuropeptide inactivation, as illustrated in the case of enkephalins' (1)(2)(3)(4)(5). In contrast, the study of the fate of endogenous neuropeptides released by depolarization of brain slices allows the physiologically relevant peptidases (20)(21)(22) and characteristic peptide fragments they produce (23) to be identified. The main advantage of this system is that, by retaining much of the integrity of the native tissue, the released peptide (in near-physiological concentrations) comes into contact initially with physiologically relevant peptidases presumably located close to the nerve endings from which'the peptide originates.…”