ISOLATION AND PARTIAL CHARACTERIZATION OF AN OPIOID-LIKE 88 KDA HIBERNATION-RELATED PROTEIN

Previous studies show that infusion of hibernating woodchuck albumin ( HWA) induces hibernation in summer-active ground squirrels and results in profound behavioral and physiological depression in primates. Thes e effects are reversed by the administration of opiate antagonists, su ggesting that the putative hibernation induction trigger (HIT) may act through opioid receptors. We have demonstrated that both HIT-containi ng plasma and the synthetic alpha opioid D-Ala(2)-D-Leu(5)-enkephalin (DADLE), which mimics the activity of HIT in hibernators, extend tissu e survival time of a multi-organ autoperfusion system by 3-fold. In th is study we present the first data showing biological activity with a much more highly purified plasma fraction from hibernating woodchucks, identified as the hibernation-related factor (HRF). Both the HRF and DADLE show opiate-like contractile inhibition in the mouse vas deferen s (Mvd) bioassay. We also have preliminary evidence in an isolated rab bit heart preparation indicating that the HRF and DADLE act similarly to restore left ventricular function following global myocardial ische mia. Furthermore, we have partially sequenced an alpha 1-glycoprotein- like 88 kDa hibernation-related protein (p88 HRP) present in this frac tion, which may prove to be the blood-borne HIT molecule. (C) 1998 Els evier Science Inc. All rights reserved.