Differential control of somatostatin messenger RNA in rat gastric corpus and antrum. Role of acid, food, and capsaicin-sensitive afferent neurons.

Abstract

Somatostatin messenger RNA in the antrum and corpus of rat stomach was quantified by Northern and slot blotting using a probe generated by the polymerase chain reaction. Fasting for 48 h enhanced the abundance of somatostatin mRNA in the pyloric antral region, but not in the acid-secreting region of the stomach. In fasted rats, somatostatin mRNA in antrum, but not corpus, was decreased by inhibition of acid secretion with omeprazole. In contrast, in rats treated with capsaicin to lesion small diameter afferents there was a significant decrease in somatostatin mRNA abundance in the corpus but not antrum. The effects of capsaicin cannot be attributed to nonspecific changes in gastric endocrine cell gene expression, since the abundance of histidine decarboxylase mRNA (which is a functionally regulated marker for a different gastric endocrine cell type) did not change with capsaicin. Gastric capsaicin-sensitive afferents are rich in calcitonin gene-related peptide, and in rats with antibodies to this peptide there was reduced corpus somatostatin mRNA. Moreover, infusion of calcitonin gene-related peptide in control rats produced a significant increase in somatostatin mRNA in the gastric corpus. The results indicate that somatostatin mRNA abundance is controlled by the gastric luminal contents and the extrinsic afferent innervation, but the relative importance of these factors differs in antrum and corpus: luminal contents are relatively more important in antrum and primary afferents using calcitonin gene-related peptide in the corpus. (J. Clin. Invest. 1993. 91:244-250.)

Pdx1inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells

“…Approximately 90% of intestinal Sst is present in the mucosa, whereas 10% is present in the muscular layer (44). Given that there is evidence suggesting that the Sst gene is differentially regulated in different populations of Sst-producing cells in the stomach (16,49), it would be of interest to investigate whether the same pancreasspecific TSE I and TSE II elements in the Sst gene promoter or other regulatory sequences mediate Pdx1 regulation in the proximal small intestine.…”

Food stimulation of histidine decarboxylase messenger RNA abundance in rat gastric fundus.

“…However, while both plasma gastrin and HDC increased promptly after refeeding, gastrin immunoneutralization did not reduce HDC mRNA abundance after 30 min refeeding, which suggests that while gastrin might control HDC mRNA over periods of a few hours, or longer, there is at least one meal-induced factor that regulates gastric HDC over shorter periods, e.g. < 1 h. The changes in HDC mRNA with fasting are unlikely to reflect a general reduction in mRNA levels because rats treated similarly showed no change in fundic somatostatin mRNA levels, and an increase in antral somatostatin mRNA levels was observed (Wu, Sumii, Tari, Mogard & Walsh, 1990;Sandvik, Dimaline, Forster & Dockray, 1993 (Campbell & Yamada, 1989). Moreover, refeeding of fasted rats produced rapid changes in gastrin and somatostatin mRNA abundance over intervals comparable to those described for postprandial HDC mRNA described here (Wu, Sumii, Tari, Wu, Sumii, Tari, Sumii & Walsh, 1991).…”

Molecular control of peptide hormone and receptor expression

“…The corpus D-cell is of the closed type and, therefore, would not be expected to communicate directly with gastric lumen contents. Rats made achlorhydric for 48 h showed 3-or 4-fold decreases in antral somatostatin mRNA abundance, but corpus levels were virtually unchanged Sandvik et al 1993). Corpus D-cells were also relatively unaffected by food withdrawal, which at least doubled antral somatostatin mRNA abundance within 48 h Sandvik et al 1993).…”

“…1). Achlorhydria induces secondary hypergastrinaemia by dramatically reducing somatostatin biosynthesis and secretion (Brand & Stone, 1988;Wu et al 1990;Sandvik et al 1993). Administration of a specific gastrin antagonist (CI988) reversed the effect of omeprazole, suggesting that in these circumstances HDC mRNA is regulated largely by gastrin (Dimaline & Sandvik, 1991).…”

“…Corpus somatostatin mRNA abundance was halved in capsaicin-treated rats, compared with vehicle-treated controls, and was also depressed in rats actively immunoneutralized against CGRP (Sandvik et al 1993). Moreover, corpus somatostatin mRNA was elevated by CGRP infusion in conscious rats (Sandvik et al 1993). It is well established that CGRP has important functions in gastric mucosal protection, including increasing mucosal blood flow and inhibiting gastric acid secretion (Holzer, 1994); it now seems that some of these actions might be mediated by stimulating corpus somatostatin biosynthesis.…”