Isolation and partial characterization of an opioid-like 88 kDa hibernation-related protein |
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| Authors: | Noel D Horton Dimitra J Kaftani David S Bruce Evans C Bailey Alan S Krober Jeffrey R Jones Mitchell Turker Nada Khattar Tsung-Ping Su Steven F Bolling Peter R Oeltgen |
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| Affiliation: | aDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA;bDepartment of Pathology, University of Kentucky, Lexington, KY, USA;cDepartment of Biology, Wheaton College, Wheaton, IL, USA;dOregon Health Sciences University, Portland, OR, USA;eNational Institute on Drug Abuse, Baltimore, MD, USA;fDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA;gLexington V.A. Medical Center, Lexington, KY, USA |
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| Abstract: | 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. These effects are reversed by the administration of opiate antagonists, suggesting that the putative hibernation induction trigger (HIT) may act through opioid receptors. We have demonstrated that both HIT-containing plasma and the synthetic α opioid -Ala2--Leu5-enkephalin (DADLE), which mimics the activity of HIT in hibernators, extend tissue survival time of a multi-organ autoperfusion system by 3-fold. In this 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 deferens (Mvd) bioassay. We also have preliminary evidence in an isolated rabbit heart preparation indicating that the HRF and DADLE act similarly to restore left ventricular function following global myocardial ischemia. Furthermore, we have partially sequenced an α 1-glycoprotein-like 88 kDa hibernation-related protein (p88 HRP) present in this fraction, which may prove to be the blood-borne HIT molecule. |
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| Keywords: | Hibernation Opioid HIT Opiate antagonist Glycoprotein δ Opiate receptor Woodchuck RT-PCR |
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