Multiple Opioid Receptors in Endotoxic Shock: Evidence for δ Involvement and μ --δ Interactions in vivo

The use of selective δ and μ opioid antagonists has provided evidence that δ opioid receptors within the brain mediate the endogenous opioid component of endotoxic shock hypotension. The selectivity of these δ and μ antagonists was demonstrated by their differing effects upon morphine analgesia and endotoxic hypotension. The μ antagonist β -funaltrexamine, at doses that antagonized morphine analgesia, failed to alter shock, whereas the δ antagonist M 154, 129: [N, N-bisallyl-Tyr-Gly-Gly-Ψ -(CH2S)-Phe-Leu-OH] (ICI) reversed shock at doses that failed to block morphine analgesia. Therefore, selective δ antagonists may have therapeutic value in reversing circulatory shock without altering the analgesic actions of endogenous or exogenous opioids. Additional data revealed that prior occupancy of μ binding sites by irreversible opioid antagonists may allosterically attenuate the actions of antagonists with selectivity for δ binding sites. For endogenous opioid systems, this observation provides an opportunity to link in vivo physiological responses with receptor-level biochemical interactions.