title: Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human skin fibroblasts.
abstract: It has been speculated that gap junctional intercellular communication (GJIC), an intercellular signalling pathway, is involved in embryogenesis by coupling compartments of the same developmental potential. We found that thalidomide induces GJIC in human fibroblasts after activation by liver microsomes in concentrations as low as 10(-7) M. Treatment of cells with the thalidomide analog EM-12 increased GJIC without prior activation. No alteration of GJIC was detected with phthalimide and glutamate, the components of thalidomide. However, 2-phthalimido glutaric 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 related compounds.
authors.affiliation: Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Nicolai
authors.forename: H
authors.initials: H
authors.lastname: Sies
authors.forename: W
authors.initials: W
authors.lastname: Stahl
mesh_terms: D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: C001079:2-(2,6-dioxopiperidin-3-yl)phthalimidine; D013792:Thalidomide; C027948:supidimide