cAMP regulates gastrin gene expression.

Gastrin is one of the most potent regulators of acid secretion and gastrointestinal cell growth. A variety of signals regulate gastrin release from the antral G cell. However, whether these secretagogues also stimulate gastrin gene expression has not been established. Dramatic increases in gastrin gene expression occur in the stomach after birth and in response to chronic achlorhydria. Moreover, gastrin gene expression in malignant islet cell tumors (gastrinomas) appears to represent reactivation of the fetal pattern of expression in the pancreas. Thus differential expression of the gastrin gene is a reflection of differences in transcriptional control. Since various luminal and humoral factors stimulate the production of cAMP and gastrin secretion in both gastrinoma and antral G cells, we studied the effect of cAMP on gastrin gene expression. Using stable and transient transformants of a pituitary cell line containing the human gastrin gene, we found that cAMP stimulates a three-fold increase in gastrin mRNA levels and that the response maps to elements located between -148 and -40 base pairs upstream from the cap site. Collectively, these studies link an important regulator of gastrin secretion to regulation of gastrin gene expression.