title: Effects of nipradilol, a nitric oxide-releasing beta-adrenoceptor blocking agent, on phosphoenolpyruvate carboxykinase gene transcription in a rat hepatoma cell line.
abstract: Effects of nipradilol, a beta-adrenoceptor blocker with a nitroxy moiety, on phosphoenolpyruvate carboxykinase (PEPCK) gene transcription were examined using a rat hepatoma cell line, H4IIE cells. Dexamethasone was employed as an enhancer of PEPCK gene transcription. Nipradilol, but not timolol (a beta-blocker without a nitroxy moiety), attenuated PEPCK gene transcription both in the control and the dexamethasone-treated cells. The effects of nipradilol were eradicated by methylene blue (an inhibitor of cellular guanylate cyclase). Nipradilol is a unique beta-blocker that suppresses PEPCK gene transcription in hepatocytes likely through liberation of nitric oxide and resultant activation of guanylate cyclase.
authors.affiliation: Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. keishi@hsp.md.shinshu-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Yamauchi
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: S
authors.initials: S
authors.lastname: Ikeo
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Komatsu
authors.forename: T
authors.initials: T
authors.lastname: Aizawa
authors.forename: K
authors.initials: K
authors.lastname: Hashizume
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D013999:Timolol / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000319:Adrenergic beta-Antagonists; D007328:Insulin; D011412:Propanolamines; D009569:Nitric Oxide; D003907:Dexamethasone; D013999:Timolol; D019764:Phosphoenolpyruvate Carboxykinase (ATP); C036089:nipradilol; D008751:Methylene Blue