title: Regulation of vasopressin messenger RNA levels in the small cell lung carcinoma cell line GLC-8: interactions between glucocorticoids and second messengers.
abstract: The role of glucocorticoids and second messenger systems in the regulation of the vasopressin (VP) gene was studied in the human small cell lung carcinoma cell line GLC-8. Small cell lung carcinoma GLC-8 cells express VP mRNA and contain both glucocorticoid and mineralocorticoid receptors. Treatment with the synthetic glucocorticoid dexamethasone when added alone at 10(-8) M had no effect on the VP mRNA level and decreased the level by 30% at 10(-6) M. However, the effect of dexamethasone changed to positive when cells were simultaneously treated with cAMP-enhancing agents. VP mRNA levels, which were elevated by 1.5- to 2-fold by the cAMP-enhancing agents alone, increased a further 1.5- to 3-fold by dexamethasone. Thus, the combined effect of dexamethasone and cAMP stimulation was a 3- to 7.5-fold increase in VP mRNA levels. Long term treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) reduced the VP mRNA level by 75%. The TPA-suppressed VP mRNA levels could be up-regulated about 6-fold by simultaneous treatment with 8-bromo-cAMP. Dexamethasone did not alter the TPA-suppressed VP mRNA levels. These results indicate that both cAMP and protein kinase-C pathways as well as glucocorticoid receptors are involved in the regulation of VP mRNA levels and that these factors interact. This leads to a negative or positive response of VP gene expression to glucocorticoids in a state-dependent manner. The interactions may be of significance in a physiological context and relate to the different regulation of VP-expressing systems in the brain.
authors.affiliation: Rudolf Magnus Institute, Department of Pharmacology Medical Faculty, University of Utrecht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Verbeeck
authors.forename: W
authors.initials: W
authors.lastname: Sutanto
authors.forename: J P
authors.initials: JP
authors.lastname: Burbach
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014667:Vasopressins / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014667:Vasopressins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000450:Aldosterone; D003907:Dexamethasone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine; D006854:Hydrocortisone