EFFECTS OF SYNTETIC CANNABINOID RECEPTOR LIGANDS WIN 55.212-2 AND ANANDAMID UPON IN VITRO ACTIVITY OF IMMUNOCOMPETENT CELLS

Abstract

Abstract. Ability of cannabinoid receptor ligands WIN 55.212-2 and anandamid to inhibit synthesis of TNFα and IL-8 was studied in healthy donors and men with allergic disorders. To establish mechanism of action for investigated substances, the selective antagonists of the СВ1-receptor (SR141716A) and for СВ2 - receptor (SR144528) were applied. Studies with whole blood dilutions allowed of approximating in vivo conditions when investigating biological properties of WIN-55.212-2 and anandamid. The synthetic cannabinoids WIN - 55.212-2 and anandamid at a concentration of 3-10 μМ were capable of reducing synthesis of TNFα and IL-8 in lipopolysaccharide-stimulated blood leukocytes, both from healthy donors and subjects with allergic disorders. It was revealed that the antagonist of СВ1-receptor (SR141716A) did not exert a receptor-mediated effect for WIN-55.212-2 and anandamid. Meanwhile, a СВ2-receptor antagonist (SR144528) entirely eliminated completely the blocking effect of anandamid and WIN-55.212-2.

Keywords

• immune cells
• tnfα
• il-8
• cannabinoid receptor ligands
• win-55.212-2
• anandamid