STIMULATION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY THALIDOMIDE AND THALIDOMIDE ANALOGS IN HUMAN SKIN FIBROBLASTS

It has been speculated that gap junctional intercellular communication (GJIC), an intercellular signalling pathway, is involved in embryogen esis by coupling compartments of the same developmental potential. We found that thalidomide induces GJIC in human fibroblasts after activat ion by liver microsomes in concentrations as low as 10(-7) M. Treatmen t of cells with the thalidomide analog EM-12 increased GJIC without pr ior activation. No alteration of GJIC was detected with phthalimide an d glutamate, the components of thalidomide. However, 2 phthalimido glu taric acid (PGA), a hydrolysis product of thalidomide, stimulated GJIC without activation at concentrations between 10(-10) M and 10(-5) M. We suggest modification of GJIC as a biochemical mechanism responsible for pharmacological and toxicological properties of thalidomide and r elated compounds. (C) 1997 Elsevier Science Inc.