Inhibition of gastrin gene expression by somatostatin.

Abstract

Previous studies performed in this laboratory have demonstrated somatostatin-containing cells in close proximity to gastrin cells in antral mucosa and have shown that somatostatin exerts a local regulatory effect on gastrin release. The present studies were directed to determine whether the effects of somatostatin on the antral gastrin cell involve pretranslational events. The effects of somatostatin on gastrin mRNA were determined by dot blot hybridization using a gastrin antisense RNA probe derived from human gastrin cDNA. Inclusion of somatostatin in the incubation medium caused a dosedependent inhibition of steady-state gastrin mRNA. Conversely, when antral somatostatin was neutralized by the addition of specific somatostatin antibodies to the incubation medium, gastrin mRNA levels increased by 116±31% over control values (P < 0.01). Northern blot hybridization of total antral RNA demonstrated a single major band with a molecular size of -620 nucleotides, closely matching the predicted size of gastrin mRNA. The effect of somatostatin on the rate of gastrin gene transcription was examined using nuclear run-off transcription assays. Inclusion of antibodies to somatostatin in the incubation medium resulted in a 33.8±3.3% increase in gastrin gene transcriptional activity (P < 0.01). These studies indicate that, in addition to its established effect on peptide release, somatostatin exerts inhibitory effects on antral gastrin cells at the pretranslational level. Although this inhibition appears to occur in part at the gene transcriptional level, the results also indicate that somatostatin may affect posttranscriptional processing of gastrin mRNA.

Peripheral PACAP inhibits gastric acid secretion through somatostatin release in mice

“…Although the five somatostatin receptor subtypes are localized in the stomach (Prinz et al, 1994;Le Romancer et al, 1996;Krempels et al, 1997;Sternini et al, 1997;Schindler & Humphrey, 1999), functional in vivo studies in rats, dogs, and mice as well as in vitro studies in human, rat, and dog antral tissue suggest that somatostatin effects on gastric acid secretion are mediated through the activation of SSTR2 receptors located primarily on ECL cells, where they inhibit the release of histamine (Rossowski et al, 1994;Lloyd et al, 1995;Zaki et al, 1996;Aurang et al, 1997;Fung & Greenberg, 1997;Martinez et al, 1998;Patel, 1999;Martinez, 2002;Piqueras et al, 2003b). In addition, somatostatin also regulates gastrin gene expression and gastrin release from G cells (Karnik et al, 1989;Chiba & Yamada, 1994). In vitro studies in canine antral G cells suggest that modulatory effects of somatostatin on gastrin release are also mediated through SSTR2 receptors .…”

Octreotide inhibits the enterochromaffin-like cell but not peroxisome proliferator-induced hypergastrinemia

“…In the stomach, D cells are located in proximity to their target cells, and exert a restraint on the secretion of histamine and gastrin (Saffouri et al 1980, Sandvik & Waldum 1988, Karnik et al 1989. Receptors for somatostatin are found on ECL and G cells (Borin et al 1996, Zaki et al 1996.…”

Detection of gastrin mRNA in human antral mucosa and digestive endocrine tumors by in situ hybridization: a correlative study with immunocytochemistry and electron microscopy.

“…Most of these studies have used molecular hybridization techniques such as Northern and dot-blots. They have been conducted with gastrin anti-sense RNA probes to analyze either the regulation of gastrin mRNA in antral mucosa of animals under several conditions, especially under omeprazole treatment (26)(27)(28), or the gastrin gene expression during neonatal development in the rat (29). To our knowledge, only two studies have used in situ hybridization to localize gastrin mRNA transcripts in tissue.…”