Gastric ECL cells release histamine in response to food due to 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 hrs, 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 24hrs fasted rats, thereby eliminating mRNA contamination from other gastric mucosal cell types, identified significant increased gene expression of the enzymes histidase and urocanase catabolizing the HDC substrate L-histidine, but significant decreased expression of the cellular L-histidine uptake transporter SN2 and of the vesicular monoamine transporter 2 responsible for histamine uptake into secretory vesicles. This was confirmed by RT-qPCR of gastric fundic mucosal samples from fed and 24 hrs fasted rats. The decrease of VMAT2 gene expression was also shown by a decrease in VMAT2 protein content in protein extracts from fed and 24 hrs fasted rats compared to equal amounts of HDC protein and NaK-ATPase 1 subunit protein content. These results indicate that rat gastric ECL cells regulate their histamine content during 24 hrs 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.