Novel non-peptidic opioid compounds with immunopotentiating effects.

Abstract

Central nervous system mediated indirect effect of opioids have been shown to suppress immune function when administered through a central loci such as the periaqueductal gray region of the mesencephalon.(1-4) Paradoxically, the direct effect of opioids on leukocytes enhance, suppress, or have no effect on in vitroparameters of immune function. It is widely accepted that opioids play an immunomodulatory role both in vivo and in vitro. (1)Three distinct types of neuronal opioid receptors, e, δ, and K, have been cloned and sequenced which account for the pharmacological distinctions.(5) With the cloning of opioid receptors on leukocytes we are able to examine the direct effects of opioids on immune cells.(6-9) However, classical neuronal opioid receptor characterization may not be appropriate.(3, vn6, 9-12) Leukocyte activation, natural killer cell activity and altered monocyte chemotaxis have been shown to be altered by the direct effect of opioids on leukocytes. (13-17) We have focused on the direct effect of opioids on cells of the immune system. Cloning of both neural- and immune-derived opioid receptors will assist in the discovery of the molecular mechanisms underlying this pathway.