ALUNG June 20/6

Guo, Yihe, Cara Martinez-Williams, Kirk A. Gilbert, and D. Eugene Rannels. Inhibition of gap junction communication in alveolar epithelial cells by 18a-glycyrrhetinic acid. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L1018– L1026, 1999.—Cultured alveolar epithelial cells exhibit gap junction intercellular communication (GJIC) and express regulated levels of connexin (Cx) 43 mRNA and protein. Newly synthesized radiolabeled Cx43 protein equilibrates with phosphorylated Cx43 isoforms; these species assemble to form both connexons and functional gap junction plaques. The saponin 18a-glycyrrhetinic acid (GA) rapidly and reversibly blocks GJIC at low concentrations (5 μM). Extended exposure to 18a-GA at higher concentrations causes inhibition of GJIC and timeand dose-dependent reductions in both Cx43 protein and mRNA expression. The latter toxic effects are paralleled by disassembly of gap junction plaques and are reversed less readily than acute effects on GJIC. These observations demonstrate 18a-GA-sensitive regulation of intercellular communication in epithelial cells from the mammalian lung and suggest a role for Cx43 expression and phosphorylation in acute and chronic regulation of GJIC between alveolar epithelial cells.