Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions

Opioid receptors have been reported on immune cells of several species and shown to subserve effector functions of these cell types. Mu-selective opio id agonists such as morphine are immunosuppressive, whereas certain 6-opioi d receptor-selective agonists have been associated with immunopotentiation. We have previously shown that intracerebroventricular administration of th e non-peptidic 6-opioid receptor agonists did not alter certain parameters of immunocompetence. In this study, we evaluated the in vitro effects of th e novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahy-droquin oline (CGPM-9) on lymphocyte and macrophage functions. We demonstrated that CGPM-9 enhanced rat thymic lymphocyte proliferative response to concanaval in A (2.85- to 5.5-fold increases), and suppressed LPS-induced nitric oxide (67 to 72 percent reduction) and TNF-alpha production (46 percent reductio n) by peritoneal macrophages, compared with untreated control. The mu -opio id receptor selective antagonist CTOP used at equimolar doses, significantl y suppressed the effect of CGPM-9 on lymphocyte and macrophage functions (C TOP alone did not show any effect on lymphocyte or macrophage functions). I n summary, CGPM-9 activated thymic lymphocyte proliferation and suppressed macrophage functions by acting at mu -opioid receptors. This suggests that opioid receptors on immunocytes may be coupled to different signaling pathw ays depending on the cell type and effector function being analyzed. The me chanism(s) associated with the differential effect of CGPM-9 on these immun e cells remains to be elucidated. The pharmacotherapeutic potential for com pounds such as CGPM-9 which potentiate T lymphocyte proliferation and suppr ess production of macrophage-derived inflammatory cytokines is substantial in research and clinical medicine. (C) 2001 Elsevier Science Inc. All right s reserved.