Autoimmunovascular regulation: morphine and anandamide and ancondamide stimulated nitric oxide release.

The hypothesis concerning morphine as an endogenous signal molecule has been strengthened with the recent discovery of a new opiate receptor subtype, designated mu3. This opiate receptor is opiate alkaloid sensitive and opioid peptide insensitive, including peptides previously shown to have affinities for mu opiate receptors. This receptor is coupled to nitric oxide release in human endothelial cells, granulocytes and monocytes and in invertebrate immunocytes and microglia. In relation to the endothelium, it has also been coupled to vasodilation via nitric oxide. Given the known influence of nitric oxide in downregulating cell adhesion, the role of this compound has now been investigated in also diminishing endothelial-immunocyte interaction. Morphine, via nitric oxide, has the potential to diminish adhesion molecule expression and in so doing calm an inflammatory process between immunocytes and the endothelial surface. In this regard, the potential for abuse is also present.