1. Fasting-induced changes in ECL cell gene expression.
- Author
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Lambrecht NW, Yakubov I, and Sachs G
- Subjects
- Amino Acid Transport Systems, Neutral biosynthesis, Amino Acid Transport Systems, Neutral genetics, Animals, Cell Count, Enzyme Induction, Gene Expression Profiling, Histamine metabolism, Histamine Release physiology, Histidine Ammonia-Lyase biosynthesis, Histidine Ammonia-Lyase genetics, Histidine Decarboxylase metabolism, Male, RNA, Messenger biosynthesis, RNA, Messenger genetics, Rats, Rats, Sprague-Dawley, Sodium-Potassium-Exchanging ATPase biosynthesis, Sodium-Potassium-Exchanging ATPase genetics, Transcription, Genetic, Urocanate Hydratase biosynthesis, Urocanate Hydratase genetics, Vesicular Monoamine Transport Proteins biosynthesis, Vesicular Monoamine Transport Proteins genetics, Enterochromaffin Cells metabolism, Fasting metabolism, Gene Expression Regulation physiology, Histamine Release genetics
- Abstract
Gastric enterochromaffin-like (ECL) cells release histamine in response to food because of elevation of gastrin and neural release of pituitary adenylate cyclase-activating peptide (PACAP). Acid secretion is at a basal level in the absence of food but is rapidly stimulated with feeding. Rats fasted for 24 h showed a significant decrease of mucosal histamine despite steady-state expression of the histamine-synthesizing enzyme histidine decarboxylase (HDC). Comparative transcriptomal analysis using gene expression oligonucleotide microarrays of 95% pure ECL cells from fed and 24-h fasted rats, thereby eliminating mRNA contamination from other gastric mucosal cell types, identified significantly increased gene expression of the enzymes histidase and urocanase catabolizing the HDC substrate L-histidine but significantly decreased expression of the cellular L-histidine uptake transporter SN2 and of the vesicular monoamine transporter 2 (VMAT-2) responsible for histamine uptake into secretory vesicles. This was confirmed by reverse transcriptase-quantitative polymerase chain reaction of gastric fundic mucosal samples from fed and 24-h fasted rats. The decrease of VMAT-2 gene expression was also shown by a decrease in VMAT-2 protein content in protein extracts from fed and 24-h fasted rats compared with equal amounts of HDC protein and Na-K-ATPase alpha(1)-subunit protein content. These results indicate that rat gastric ECL cells regulate their histamine content during 24-h fasting not by a change in HDC gene or protein expression but by regulation of substrate concentration for HDC and a decreased histamine secretory pool.
- Published
- 2007
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