Accession Number:

ADA278136

Title:

Characterization and Utilization of Opiate-Like Hibernation Factors.

Descriptive Note:

Midterm rept. 15 Jul 92-15 Dec 93,

Corporate Author:

KENTUCKY UNIV LEXINGTON DEPT OF PATHOLOGY

Personal Author(s):

• Oeltgen, Peter R.

Report Date:

1993-12-08

Pagination or Media Count:

69.0

Abstract:

A hibernation induction trigger HIT molecule derived from the plasma of deeply hibernating woodchucks exerts profound effects mimicking a hibernation-like state when infused I.C.V. or I.V. in primates. The profound opiate-like behavioral and physiological depression occurring shortly after the infusion of the HIT-containing albumin fraction include hypothermia, bradycardia, long-term hypophagia and markedly depressed renal function. All of the aforementioned effects are reversed or retarded by the infusion of the opiate antagonists, naloxone and naltrexone. Such evidence enforces our hypothesis that the HIT molecule is not specific for hibernators, but that it may initiate its action through specific opioid receptors. We have shown that only DADLE, a delta class of opiate, could induce hibernation in summer-active ground squirrels the traditional bioassay in a fashion similar to those injected with HIT. Such evidence indicates that this delta opioid mimics the action of the HIT molecule and may be intimately involved in natural winter and summer-induced hibernation. Recently, we have developed a rapid in vitro bioassay utilizing the criteria of DNA and protein synthesis inhibition to monitor the metabolic inhibitory activity of hibernating plasma, and plasma fractions as well as the metabolic effects of the delta opioids DADLE and D-Pen 2.5-Enkephalin DPDPE. Hibernation induction, TriggerHIT, Woodchucks, Delta opioidsD-Ala -Leu--Enkephalin D-Pen 2,5-Enkephalin--DPDPE, Multiorgan Autoperfusion System, Metabolic Inhibition3H-Thymidine uptake, 14C-Leucine uptake.

Descriptors:

• *CLINICAL MEDICINE
• *LIFE SUPPORT SYSTEMS
• *ARTIFICIAL RESPIRATION
• FUNCTIONS
• SYNTHESIS
• DEOXYRIBONUCLEIC ACIDS
• WINTER
• ANTIBODIES
• MONITORS
• PRESERVATION
• KIDNEYS
• TRIGGER CIRCUITS
• BIOASSAY
• PHARMACOLOGICAL ANTAGONISTS
• ALBUMINS
• SUMMER
• TRANSPLANTATION
• HYPOTHERMIA
• GELS
• THYMIDINES
• SQUIRRELS
• LEUCINE
• INFUSIONS
• DELTAS
• BRADYCARDIA
• INHIBITION
• PRIMATES
• ALUMINUM ARSENIDES
• LUNG
• TIME
• MOLECULES
• PROTEINS

Subject Categories:

• Biochemistry
• Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE