Fasting-induced changes in ECL cell gene expression

• Published in: Physiological genomics 2007-10, Vol.31 (2), p.183-192
• Main Authors: Lambrecht, Nils W. G, Yakubov, Iskandar, Sachs, George
• Format: Article
• Language: English
• Subjects: Amino Acid Transport Systems, Neutral - biosynthesis; Amino Acid Transport Systems, Neutral - genetics; Animals; Cell Count; Enterochromaffin Cells - metabolism; Enterochromaffin Cells - secretion; Enzyme Induction; Fasting - metabolism; Gene Expression Profiling; Gene Expression Regulation - physiology; Histamine - metabolism; Histamine Release - genetics; Histamine Release - physiology; Histidine Ammonia-Lyase - biosynthesis; Histidine Ammonia-Lyase - genetics; Histidine Decarboxylase - metabolism; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; 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
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00252.2006

1 Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 2 Department of Physiology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 3 Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 4 Membrane Biology Laboratory, West Los Angeles Department of Veterans Affairs Medical Center, Los Angeles, California 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 histamine 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 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. enterochromaffin-like cell; oligonucleotide expression microarray; transcriptome; histamine; secretion