Alternative strategy for stress tolerance: opioids.
Endogenous opioids have been implicated in the pathway of tolerance to stresses. Hibernating tissues tolerate stress. Serum from hibernating woodchucks (hibernation induction trigger [HIT]), from summer nonhibernating animals (summer woodchuck active plasma [SWAP], and potential "hibernation opioid mimics" (D-Ala(2) D Leu(5) Enkephalin [DADLE]), and Deltorphin D (Delt D) were used as ischemic preconditioning agents (IPC) in an in vivo surgically induced cardiac ischemia rat model. Comparison of the IPC treatment was monitored by the molecular intensity of stress transcripts for polyubiquitin and HSP70 in Northern blot analyses. Delt D and HIT significantly reduced total polyubiquitin transcript expression, 2.1-fold and 1.4-fold, respectively, in ischemic tissue, while SWAP and DADLE did not differ from saline controls. The Delt D effect was sensitive to glibenclamide (Glb), a K(ATP) (potassium adenosine triphosphate) channel blocker. No inducible HSP70 was detected. The demonstration of an opioid IPC modulation of the ubiquitin stress pathway found here may be relevant for development of drug intervention in heart attacks and stroke.
Sonneborn
Joan Smith
JS
Department of Zoology & Physiology, University of Wyoming, Laramie 82071-3166, USA. cancun@uwyo.edu
Gottsch
Henry
H
Cubin
Eric
E
Oeltgen
Peter
P
Thomas
Paul
P
D000818:Animals; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008392:Marmota / Q000097:blood; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D010455:Peptides; D011506:Proteins / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology*
D009842:Oligopeptides; D018847:Opioid Peptides; D010455:Peptides; D011506:Proteins; C036932:hibernation induction trigger; C059567:deltorphin; D016308:Enkephalin, Leucine-2-Alanine