title: Fasting-induced changes in ECL cell gene expression.
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.
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. nilslam@ucla.edu
authors.forename: Nils W G
authors.initials: NW
authors.lastname: Lambrecht
authors.forename: Iskandar
authors.initials: I
authors.lastname: Yakubov
authors.forename: George
authors.initials: G
authors.lastname: Sachs
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002452:Cell Count; D004759:Enterochromaffin Cells / Q000378:metabolism*; D004790:Enzyme Induction; D005215:Fasting / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006632:Histamine / Q000378:metabolism; D006636:Histamine Release / Q000235:genetics* / Q000502:physiology; D006638:Histidine Ammonia-Lyase / Q000096:biosynthesis / Q000235:genetics; D006640:Histidine Decarboxylase / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D014559:Urocanate Hydratase / Q000096:biosynthesis / Q000235:genetics; D050493:Vesicular Monoamine Transport Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D012333:RNA, Messenger; C424137:SLC38A5 protein, human; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D006632:Histamine; C499075:Atp1a1 protein, rat; D006640:Histidine Decarboxylase; D014559:Urocanate Hydratase; D006638:Histidine Ammonia-Lyase; D000254:Sodium-Potassium-Exchanging ATPase