Geranylgeranylacetone stimulates mucin synthesis in cultured guinea pig gastric pit cells by inducing a neuronal nitric oxide synthase

Nitric oxide (NO) has been considered to play an important role in the regulation of blood flow, mucosal integrity, and mucus production in the stomach. We investigated the stimulatory actions of epidermal growth factor (EGF) and a cytoprotective compound, geranylgeranylacetone (GGA), on mucin synth...

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Bibliographic Details
Published in:Journal of gastroenterology 2000, Vol.35 (9), p.673-681
Main Authors: Rokutan, K, Teshima, S, Kawai, T, Kawahara, T, Kusumoro, K, Mizushima, T, Kishi, K
Format: Article
Language:English
Subjects:
Animals
Blotting, Northern
Blotting, Western
Diterpenes - pharmacology
Diterpenes - therapeutic use
Gastric Mucosa - cytology
Gastric Mucosa - drug effects
Gastric Mucosa - metabolism
Glucosamine - physiology
Guinea Pigs
Microscopy, Electron
Mucins - biosynthesis
Nitric Oxide - metabolism
Oxidoreductases - pharmacology
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Summary:Nitric oxide (NO) has been considered to play an important role in the regulation of blood flow, mucosal integrity, and mucus production in the stomach. We investigated the stimulatory actions of epidermal growth factor (EGF) and a cytoprotective compound, geranylgeranylacetone (GGA), on mucin synthesis in guinea pig gastric pre-pit cells, maintained in a serum-free culture system. GGA increased [3H]glucosamine uptake and the accumulation of mucus granules positive for galactose oxidase-Schiff reaction in the cells. This stimulatory action of GGA was equivalent to that of EGF, but GGA did not stimulate the cell growth. Both EGF and GGA increased the release of NO degeneration products, NO2- and NO3-. The [3H]glucosamine uptake was completely inhibited by the non-selective NO synthase (NOS) inhibitors, N(G)-nitro-L-arginine and N(G)-monomethyl-L-arginine, and it was only partially inhibited by a more selective inhibitor for inducible NOS isoform (iNOS), aminoguanidine. Northern blotting with a cDNA probe for rat iNOS, and Western blotting with a polyclonal antibody against iNOS, demonstrated that GGA did not up-regulate the iNOS mRNA expression nor induce its protein. In contrast, GGA and EGF induced neuronal NOS, but not endothelial NOS, which was confirmed by immunoblot analyses with antibodies against these constitutive NOS isoforms. Thus, the present experiments suggests that GGA, as well as EGF, stimulates mucin synthesis at least in part through an NO-dependent pathway, leading to an increase in the integrity of the gastric mucosa.
ISSN:0944-1174
1435-5922
DOI:10.1007/s005350070046