RT Journal Article
SR Electronic
T1 Enhancement of Proopiomelanocortin Gene Promoter Activity by Local Anesthetics in a Pituitary Cell Line
JF Regional Anesthesia & Pain Medicine
JO Reg Anesth Pain Med
FD BMJ Publishing Group Ltd
SP 60
OP 66
DO 10.1016/j.rapm.2006.10.013
VO 32
IS 1
A1 Masahiro Ikeda
A1 Masahiro Kakuyama
A1 Takehiro Shoda
A1 Kazuhiko Fukuda
YR 2007
UL http://rapm.bmj.com/content/32/1/60.abstract
AB Background and Objectives: Corticotropin-releasing hormone (CRH) induces gene expression of proopiomelanocortin, a precursor protein of adrenocorticotropic hormone and β-endorphin, by elevating intracellular cyclic adenosine 3′,5′-monophosphate (cyclic AMP) level in anterior pituitary cells and immune cells. CRH-induced proopiomelanocortin gene expression plays an important role in stress responses and is affected by a variety of drugs, but it is not known whether local anesthetics can directly affect the gene expression. We hypothesized that local anesthetics may directly affect proopiomelanocortin gene expression and can modulate production of adrenocorticotropic hormone and β-endorphin.Methods: The authors used mouse pituitary tumor cells stably transfected with approximately 0.7 kilobases of the rat proopiomelanocortin 5′ promoter linked with the luciferase gene. In the presence or absence of local anesthetics (lidocaine, mepivacaine, bupivacaine, and ropivacaine), cells were stimulated by CRH or forskolin. After stimulation, proopiomelanocortin gene promoter activity was assessed as luciferase activity, and cyclic AMP efflux was measured by enzymeimmunoassay.Results: CRH- or forskolin-stimulated proopiomelanocortin promoter activity was significantly enhanced by local anesthetics. Cyclic AMP efflux induced by CRH was not significantly increased by local anesthetics.Conclusions: It was concluded that local anesthetics potentiate the effect of CRH or forskolin on proopiomelanocortin promoter activity without changing the intracellular cyclic AMP level. It might be possible that transcriptional regulation mediated by cyclic AMP is also enhanced by local anesthetics in the other cells.