Stimulatory effects of opioid neuropeptides on locomotory activity and conformational changes in invertebrate and human immunocytes: Evidence for a subtype of δ receptor

The presence of opioid neuropeptides was shown to stimulate conformational changes and locomotory activity in immunocytes of two representatives of invertebrates as well as in human leukocytes. Cells were examined by use of phase-contrast and Nomarski optics coupled with a Zeiss Axiophot microscope, and of the Zeiss Videoplan/Vidas Image Analysis system. Immunocompetent blood cells, activated by exogenous opioids or stressful stimuli presumed to engage endogenous opioids, showed flattening, elongation, and formation of pseudopodia. In the mollusc Mytilus edulis, ameboid movements resulted in the formation of cell clusters, an activity not observed in untreated controls, or in immunocytes simultaneously exposed to opioid and naloxone. Tests with nine immunoreactive substances revealed immunocyte stimulation by δ-, μ-, κ-, and ε(?)-selective ligands. One of these, [D-Ala²-,D-Met⁵]enkephalinamide (DAMA), active at a concentration of 10 pM, proved to be considerably more effective than the rest. The high pharmacological potency of DAMA, observed in both human and invertebrate immunocytes, sets this opioid apart from the closely related [D-Ala²,D-Leu⁵]enkephalin, a discrepancy not occurring in the mammalian nervous system. This suggests a specific function for [Met]enkephalin in immunoregulation, mediated perhaps by a special subtype of δ receptor.