Delta-1 opioid agonist acutely increases hypoxic tolerance

Area of Science:

• Physiology
• Pharmacology
• Neuroscience

Background:

• Intermittent hypoxia (hypoxic conditioning) confers acute adaptation, increasing survival during subsequent hypoxic challenges.
• Opioid antagonists like naloxone, naltrindole, and BNTX block this hypoxia-induced adaptation.
• The precise opioid pathway involved in this adaptation requires further elucidation.

Purpose of the Study:

• To pharmacologically characterize the acute adaptation to hypoxia using selective opioid agonists.
• To investigate the role of specific opioid receptor subtypes in mediating hypoxic adaptation.
• To determine if activation of opioid receptors can mimic the survival-enhancing effects of hypoxic conditioning.

Main Methods:

• Administration of selective opioid agonists ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, U50488H, DPDPE) to mice.
• Assessment of survival time during hypoxic challenges after agonist administration.
• Use of selective opioid antagonists (naltrindole, BNTX) to block agonist effects.
• Measurement of body temperature changes following DPDPE administration.

Main Results:

• Selective opioid agonists further augmented the survival increase induced by hypoxic conditioning.
• DPDPE increased survival time in naive mice independently of hypoxic conditioning and decreased body temperature.
• The DPDPE-induced increase in survival was blocked by the delta-1-selective antagonist BNTX, but not by the delta-2-selective antagonist naltrindole.
• DPDPE's hypothermic effect was not blocked by either BNTX or naltrindole.

Conclusions:

• The mechanism of acute hypoxic adaptation involves an endogenous delta-1 opioid pathway.
• Activation of delta-1 opioid receptors can mimic the acute adaptation to intermittent hypoxia, enhancing survival.
• DPDPE's effects on survival and body temperature appear to be mediated by distinct pathways, with survival linked to delta-1 receptors.