title: Tumor necrosis factor alpha stimulates adenylyl cyclase activity in human myometrial cells.
abstract: Cytokines such as tumor necrosis factor alpha (TNFalpha) have been implicated in amniotic fluid infections and preterm and term labor. The underlying mechanisms are incompletely understood. In some smooth muscle cells, TNFalpha affects function of the beta-adrenergic/adenylyl cyclase pathway. The present study was performed to examine the effects of chronic TNFalpha exposure on adenylyl cyclase activity in cell cultures of human myometrium. Chronic TNFalpha exposure led to a dose- and time-dependent increase in basal-, GTP-, NaF-, and forskolin-stimulated adenylyl cyclase (AC) activity. The increase in AC activity was not mediated by changes in the expression of the heterotrimeric G proteins G(s)alpha or G(i)alpha as determined by immunoblotting. In addition, increases in AC activity occurred in the presence of indomethacin, indicating that these changes were not provoked by TNFalpha-induced changes in prostaglandin production. The present results suggest that TNFalpha-induced increases in AC activity in human myometrial cells obtained from the lower uterine segment occur at the level of G-protein/AC interaction or at the level of the AC enzyme itself.
authors.affiliation: Department of Anesthesiology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Gogarten
authors.forename: Karen S
authors.initials: KS
authors.lastname: Lindeman
authors.forename: Carol A
authors.initials: CA
authors.lastname: Hirshman
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000096:biosynthesis; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007213:Indomethacin / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D007213:Indomethacin