Individual variability in Tyr-Gly-Gly formation from enkephalin hydrolysis in mouse plasma

We examined the effects of captopril (an angiotensin-converting enzyme inhibitor) and phosphoramidon (a selective enkephalinase inhibitor) on Tyr-Gly-Gly production during Met-enkephalin hydrolysis in plasma samples taken from individual outbred Swiss-Webster and inbred C57BL/6J and DBA/2J mice. Discriminant analysis procedures identified three distinct plasma profiles of Tyr-Gly-Gly production in all strains of mice: a captopril-sensitive/phosphoramidon-insensitive profile, a captopril-insensitive/phosphoramidon-sensitive profile, and a moderate captopril and phosphoramidon sensitivity profile. The abilities of captopril and phosphoramidon to inhibit Tyr-Gly-Gly production in the same mouse plasma sample were highly inversely correlated (r = -0.938). Plasma of Swiss-Webster mice whose cages and bedding had been changed 24 h prior to sample collection was significantly more likely to exhibit the captopril-sensitive/phosphoramidon-insensitive profile than the plasma of mice whose cages/bedding had not been changed for at least 5 days. The results suggest that environmental novelty may dramatically alter the activity of a plasma dipeptidyl carboxypeptidase system, and thereby regulate behavioral and physiological responses to novel experiences.