Further studies on opioids and hibernation: Delta opioid receptor ligand selectively induced hibernation in summer-active ground squirrels

Oeltgen, Peter R.; Nilekani, Sita P.; Nuchols, Paula A.; Spurrier, Wilma A.; Su, Tsung‐Ping

doi:10.1016/0024-3205(88)90406-7

Cited by 119 publications

(79 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this characterization, DOPs induce a hypometabolic state of similar depth as the HIT, whereas mu-or kappa-opioid receptor agonists show no effect [97,98]. The involvement of opioid receptors is further substantiated by the inability of DOP to induce hypometabolism upon exposure to naloxon, a non-specific opioid receptor antagonist [99][100][101][102].…”

Section: Delta-opioidssupporting

confidence: 54%

The physiology of artificial hibernation

Heger

2015

JCTRes

View full text Add to dashboard Cite

Incomplete understanding of the mechanisms responsible for induction of hibernation prevent translation of natural hibernation to its artificial counterpart. To facilitate this translation, a model was developed that identifies the necessary physiological changes for induction of artificial hibernation. This model encompasses six essential components: metabolism (anabolism and catabolism), body temperature, thermoneutral zone, substrate, ambient temperature, and hibernation-inducing agents. The individual components are interrelated and collectively govern the induction and sustenance of a hypometabolic state. To illustrate the potential validity of this model, various pharmacological agents (hibernation induction trigger, delta-opioid, hydrogen sulfide, 5'-adenosine monophosphate, thyronamine, 2-deoxyglucose, magnesium) are described in terms of their influence on specific components of the model and corollary effects on metabolism. Relevance for patients: The ultimate purpose of this model is to help expand the paradigm regarding the mechanisms of hibernation from a physiological perspective and to assist in translating this natural phenomenon to the clinical setting.

show abstract

Section: Delta-opioidssupporting

confidence: 54%

The physiology of artificial hibernation

Heger

2015

JCTRes

View full text Add to dashboard Cite

show abstract

“…Hence, the formation of nuclear bodies may be another effective method of global transcriptional suppression during hibernation. Interestingly, the delta opioid D-Ala2-D-Leu5 enkephalin, which mimics the activity of the hibernation induction trigger (Oeltgen et al, 1988), delayed the disassembly of nuclear bodies during in vitro studies with G. glis liver (Malatesta et al, 2001). This provides more evidence that nuclear body formation and protein SUMOylation has a physiological function in hibernation.…”

Section: Effect Of Hibernation On Indices Of Transcriptional Control mentioning

confidence: 80%

Mammalian hibernation: differential gene expression and novel application of epigenetic controls

Morin¹,

Storey²

2009

Int. J. Dev. Biol.

101

View full text Add to dashboard Cite

This review highlights current information about the regulatory mechanisms that govern gene expression during mammalian hibernation, in particular the potential role of epigenetic controls in coordinating the global suppression of transcription. Hibernation is characterized by long periods of deep torpor (when core body temperature drops to near ambient) that are interspersed with brief arousal periods back to euthermia. Entry into torpor requires coordinated controls which strongly suppress and reprioritize all metabolic functions, including global controls on both transcription and translation. At the same time, however, selected hibernation-specific genes are up-regulated under the control of specific transcription factors to support the torpid state; this includes genes that encode proteins involved in lipid fuel catabolism and in long term cytoprotection (e.g. antioxidants, chaperones). We evaluate the currently available information on global transcriptional suppression in hibernation and propose that epigenetic mechanisms such as DNA methylation, histone modification, SUMOylation and the actions of sirtuins play crucial roles in transcriptional suppression during torpor. Global controls providing translational suppression also occur during hibernation including reversible phosphorylation control of ribosomal initiation and elongation factors as well as polysome dissociation. We also present initial data that mRNA transcripts are regulated via inhibitory interactions with microRNA species during torpor and provide the first evidence of differential expression of miRNAs in hibernators. When taken together, these mechanisms provide hibernators with multiple layers of regulatory controls that achieve both global repression of gene expression and selected enhancement of genes/proteins that achieve the hibernation phenotype.

show abstract

“…Many parallels exist between SLP and hibernation: hibernation is triggered by ␦-opioid agonism, which can also induce hibernation in nonhibernating primates (Oeltgen et al, 1982(Oeltgen et al, , 1988; ␦-opioid triggered hibernation increases stress resistance (Bolling et al, 1997); hibernating and anoxiatolerant species harness PKA signaling (Storey, 1996;Holden and Storey, 1998); and repression of Akt suppresses energy-costly anabolic/growth processes to maintain cell viability over extended periods (Cai et al, 2004;Abnous et al, 2008). The SLP phenotype is induced by ␦-opioid agonism, involves PI3K-dependent signals and repression of Akt expression (Fig.…”

Section: Discussionmentioning

confidence: 99%

Sustained Ligand-Activated Preconditioning via δ-Opioid Receptors

Peart¹,

Hoe²,

Gross³

et al. 2010

J Pharmacol Exp Ther

View full text Add to dashboard Cite

We have previously described novel cardioprotection in response to sustained morphine exposure, efficacious in young to aged myocardium and mechanistically distinct from conventional opioid or preconditioning (PC) responses. We further investigate opioid-dependent sustained ligand-activated preconditioning (SLP), assessing duration of protection, opioid receptor involvement, additivity with conventional responses, and signaling underlying preischemic induction of the phenotype. Male C57BL/6 mice were treated with morphine (75-mg subcutaneous pellet) for 5 days followed by morphine-free periods (0, 3, 5, or 7 days) before ex vivo assessment of myocardial tolerance to 25-min ischemia/45-min reperfusion. SLP substantially reduced infarction (by ϳ50%) and postischemic contractile dysfunction (eliminating contracture, doubling force development). Cardioprotection persisted for 5 to 7 days after treatment. SLP was induced specifically by ␦-receptor and not -or -opioid receptor agonism, was eliminated by ␦-receptor and nonselective antagonism, and was additive with adenosinergic but not acute morphine-or PC-triggered protection. Cotreatment during preischemic morphine exposure with the phosphoinositide-3 kinase (PI3K) inhibitor wortmannin, but not the protein kinase A (PKA) inhibitor myristoylated PKI-(14-22)-amide, prevented induction of SLP. This was consistent with shifts in total and phospho-Akt during the induction period. In summary, data reveal that SLP triggers sustained protection from ischemia for up to 7 days after stimulus, is ␦-opioid receptor mediated, is induced in a PI3K-dependent/PKA-independent manner, and augments adenosinergic protection. Mechanisms underlying SLP may be useful targets for manipulation of ischemic tolerance in young or aged myocardium.

show abstract

Further studies on opioids and hibernation: Delta opioid receptor ligand selectively induced hibernation in summer-active ground squirrels

Cited by 119 publications

References 13 publications

The physiology of artificial hibernation

The physiology of artificial hibernation

Mammalian hibernation: differential gene expression and novel application of epigenetic controls

Sustained Ligand-Activated Preconditioning via δ-Opioid Receptors

Contact Info

Product

Resources

About