RRC ID 12161
Author Rokutan K, Teshima S, Kawai T, Kawahara T, Kusumoro K, Mizushima T, Kishi K.
Title Geranylgeranylacetone stimulates mucin synthesis in cultured guinea pig gastric pit cells by inducing a neuronal nitric oxide synthase.
Journal J Gastroenterol
Abstract 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.
Volume 35(9)
Pages 673-81
Published 2000-1-1
DOI 10.1007/s005350070046
PMID 11023038
MeSH 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*
IF 6.132
Times Cited 34
DNA material Inducible NOS cDNA Rat iNOS2-2U (RDB01385)