Morphine receptors in immunocytes and neurons

Receptor interactions of morphine are reviewed, with particular attention given to a recently discovered opiate receptor, designated μ₃, with unique selectivity for morphine and certain other opiate alkaloids. Morphine, other opiate alkaloids and related analogs are known to bind to the classical σ, R and is opioid receptor subtypes. Each of these subtypes also binds one or more of the endogenous opioid peptides with high affinity. Immunocytes have recently been found to contain a unique receptor for morphine, capable of binding morphine and certain other opiate alkaloids, but with essentially no or exceedingly low affinity for the naturally occurring endogenous opioid peptides or peptide analogs. This putative μ₃ (morphine/opiate alkaloid) receptor is present in invertebrate immunocytes as well as in human peripheral blood monocytes (macrophages). More recently this same receptor has been found in certain established macrophage cell lines and in human peripheral blood granulocytes. Finally, the same or closely related opiate alkaloid-selective (μ₃) receptor has been found to be present in a neuroblastoma and in a hybrid neural cell line. Studies indicate that in the immunocytes the receptor mediates inhibitory effects of morphine on cellular chemotaxis. While the functional coupling of this receptor in neurons is not known, it is postulated that the receptor may mediate effects of opiates on neuronal differentiation and cell division as well as neuronal transmission. Both for the immune system and the nervous system, the μ₃ receptor may constitute a major site of action for putative endogenous morphine or morphine-like substances. This receptor system also provides an additional pharmacological site of action for exogenously administered opiate alkaloid drugs. The μ₃ receptor is proposed to be an important neuro-immune link. This system is likely to play a significant role in a variety of responses involving the immune system, including the response of the organism to stress, infection and malignant transformation.