The metabolic stability of the enkephalins

[Met⁵] and [Leu⁵]-enkephalins inhibit ³H-naloxone binding to brain opiate receptors much more effectively at 4°C than at 25°C. At 25°C several protease inhibitors potentiate the action of the enkephalins. Bacitracin is the most effective of these. In the presence of 100 μg/ml of bacitracin, the potencies of [Met⁵]- and [Leu⁵]-enkephalins are similar to those at 4°C. Some protease inhibitors, such as TLCK and TAME, are effective by themselves in inhibiting the binding of ³H-naloxone. Enkephalins with D-amino acids in the 2-position are equally effective at 0°C and at 25°C and their action is not potentiated by bacitracin. In particular, [D-Ala²]-enkephalins do not seem to be significantly degraded by the membrane enzymes which destroy the natural enkephalins.