Delta opioid peptide [D-Ala(2),D-Leu5]enkephalin promotes cell survival

By studying the hibernation in ground squirrels, a protein factor termed hi bernation induction trigger (HIT) was found to induce hibernation in summer -active ground squirrels. Further purification of HIT yielded an 88-kD pept ide that is enriched in winter hibernator, Partial sequence of the 88-kD pr otein indicates that it may be related to the inhibitor of metalloproteinas e. Delta opioid [DAla(2),D-Leu(5)]enkephalin (DADLE) also induced hibernati on. HIT and DADLE were found to prolong survival of peripheral organs prese rved en bloc or as a single preparation. These organs include the lung, the heart, liver a nd kidney. DADLE also promotes survival of neurons in the c entral nervous system. Methamphetamine (METH) is known to cause destruction of dopaminergic (:DA) terminals in the brain, DADLE blocked and reversed t he DA terminal damage induced by METH, DADLE acted against this effect of M ETH at least in part by attenuating the mRNA expressions of a tumor necrosi s factor p53 and an immediate early gene c-fos, DADLE also blocked the neur onal damage induced by ischemia-reperfusion following a transient middle ce rebral artery occlusion. In PC12 cells, DADLE blocked the cell death caused by serum deprivation in a naltrexone-sensitive manner. Thus, DADLE, and by extension the endogenous delta opioid peptides and delta opioid receptors, may play an important role in organ and neuronal survival. Here, critical developments concerning these fascinating cell protective properties of DAD LE are reviewed. Copyright (C) 2000 National Science Council, ROC and S. Ka rger Ag, Basel.