title: Somatostatin stimulates gastrin mRNA turnover in dog antral mucosa.
abstract: Previous studies have demonstrated that antral somatostatin exerts inhibitory effects on gastrin cells via paracrine pathways, accomplished by its release from somatostatin-containing cells into the immediate interstitial environment of the gastrin cell. The present studies were directed to examine the effect of somatostatin on gastrin gene transcription in the dog antrum and to determine whether somatostatin modulates gastrin mRNA turnover. In response to the immunoneutralization of endogenous antral somatostatin, basal gastrin gene transcriptional activity increased by 34 +/- 3.3% (p less than 0.01). Moreover, somatostatin significantly inhibited gene transcription that had been stimulated by dibutyryl-cAMP and carbachol. To determine the effect of somatostatin on gastrin mRNA turnover, antral mucosal fragments were incubated with antibodies to somatostatin, total RNA was extracted, and gastrin mRNA was measured at several time points. Following the immunoneutralization of antral somatostatin, maximum induction was achieved at 60 min, at which time gastrin mRNA levels had increased by 184 +/- 6.0% (p less than 0.01). At that time, a somatostatin analogue which is biologically active, but nonimmunoreactive with the antiserum, was added to the incubation medium. The analogue produced a prompt and steady de-induction of gastrin mRNA concentration, which returned to basal levels by 120 min. Regression analysis of RNA induction and de-induction profiles demonstrated a 292 +/- 40.6% increase (p less than 0.01) in gastrin mRNA turnover induced by somatostatin. In separate experiments antral mucosa was incubated with cycloheximide, both in the presence and absence of somatostatin antibodies. Incubation in the presence of cycloheximide resulted in a 52.3 +/- 8.4% (p less than 0.01) increase in gastrin mRNA levels under basal conditions, but had no effect following antral somatostatin immunoneutralization. Our results indicate that, although somatostatin inhibits gastrin gene transcription, its predominant effect on gastrin gene expression appears to occur at the posttranscriptional level by increasing the turnover of gastrin mRNA.
authors.affiliation: Harvard Digestive Diseases Center, Boston, Massachusetts.
authors.forename: P S
authors.initials: PS
authors.lastname: Karnik
authors.forename: M M
authors.initials: MM
authors.lastname: Wolfe
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004285:Dogs; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000235:genetics*; D015151:Immunoblotting; D066298:In Vitro Techniques; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D011706:Pyloric Antrum / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012044:Regression Analysis; D013004:Somatostatin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D005755:Gastrins; D012333:RNA, Messenger; D003609:Dactinomycin; D013004:Somatostatin; D004247:DNA; D003513:Cycloheximide