HYPOXIA DECREASES OPIOID DELTA-RECEPTOR EXPRESSION IN MOUSE-BRAIN

Delta opioid receptor activation is protective during hypoxic injury. Many adaptive responses occur during exposure to hypoxia to facilitate survival. It is possible that increased activity of the delta opioid receptor system is one such adaptation. We tested the hypothesis that mice exposed to prolonged hypoxia have increased expression of the del ta opioid receptor in brain tissue. Prolonged exposure to hypoxia (9% oxygen, balance nitrogen) continuously for seven days selectively decr eased delta opioid receptor expression in mouse brain homogenate. The same hypoxic treatment had no effects on either mu or kappa opioid rec eptor expression, indicating that this response was not due to non-sel ective degradation of protein. Shorter term hypoxic treatments (one da y and three days) did not induce changes in delta opioid receptor expr ession in whole brain homogenate. Binding assays were also conducted i n grossly dissected brain regions (cortex, midbrain, hindbrain) to det ermine whether the shorter term treatments would induce changes in rec eptor expression in more discrete areas. No consistent changes in delt a opioid receptor expression were detected in these brain regions. The se data demonstrate that opioid delta receptors are hypoxia sensitive and may be a part of an adaptive process to increase survival in the o rganism. One possible cause for the decrease in delta opioid receptor expression following seven days of hypoxic exposure may be receptor do wn-regulation caused by an increased release of endogenous substances acting at delta receptors. As delta opioid receptor agonists appear pr omising for therapeutic potential in management of hypoxic injury, cha nges in delta receptor expression in response to long-term hypoxia cou ld impact potential utilization of delta agonists in patients sufferin g chronic hypoxia.