Nitric oxide donor NOR 3 inhibits ketogenesis from oleate in isolated rat hepatocytes by a cyclic GMP-independent mechanism

Takahide Nomura, Masatsugu Ohtsuki, Shigeru Matsui, Chiho Sumi-Ichinose, Hiroko Nomura, Yasumichi Hagino

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Studies were conducted to clarify the effects of nitric oxide donors NOR 3 ((±)-(E)-ethyl-2-[(E)-hydroxyimino]5-nitro-3-bexeneamide, FK409), SIN-1 (3-morpholinosydnonimine) and SNAP (S-nitroso-N-acetylpenicillamine) on the accumulation of cGMP and cAMP and Ca2+ mobilization as well as ketogenesis from oleate in isolated rat hepatocytes. NOR 3 caused inhibition of ketogenesis from oleate along with stimulation of cGMP accumulation in rat hepatocytes, whereas SIN-1 and SNAP exerted no effect on ketogenesis despite their marked stimulation of cGMP accumulation. Although the nitric oxide trapping agent, carboxy-PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide), antagonized the stimulation by NOR 3 of cGMP accumulation, it failed to modulate the anti-ketogenic action of NOR 3. Furthermore, neither 8-bromoguanosine-3',5'-cyclic monophosphate nor N2,2'-O-dibutyrylguanosine- 3',5'-cyclic monophosphate mimicked the anti-ketogenic action of NOR 3. It is concluded in the present study that NOR 3-induced inhibition of ketogenesis in rat hepatocytes is not mediated by cGMP. The present study revealed that the remaining structure of NOR 3 from which nitric oxide had been spontaneously released had no anti-ketogenic action. We first and clearly demonstrated that nitrite production was dramatically enhanced when NOR 3 was incubated in the presence of rat hepatocytes. The mechanism whereby NOR 3 inhibits ketogenesis in rat hepatocytes will be discussed.

Original languageEnglish
Pages (from-to)40-46
Number of pages7
JournalPharmacology and Toxicology
Volume82
Issue number1
DOIs
Publication statusPublished - 1998

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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