Somatostatin-receptor 2 (sst2)-mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach.
Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst(1-5)), of which sst(2) is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst(2)-specific antagonist PRL-2903 was used. Effects of PRL-2903 on acid secretion and release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the release of histamine and gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean+/-standard error of the mean (s.e.m.). PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6+/-7.5 to 367+/-114 nM at 50 microM PRL-2903. With 10 microM PRL-2903, venous histamine output increased from baseline 6.2+/-0.5 to 20.9+/-4.9 nmol h(-1); P=0.008. The combination of 520 pM gastrin and 10 microM PRL-2903 increased venous histamine output from 41.7+/-7.3 nmol h(-1) with gastrin alone to 95.2+/-9.8 nmol h(-1); P=0.016. Further, 10 microM PRL-2903 increased acid output from baseline 8.5+/-1.8 to 37.4+/-11 micromol h(-1); P=0.017. When combined with 10 microM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4+/-14.8 to 292+/-64.2 nM; P=0.008, and gastrin concentration from 38.6+/-13.1 to 95.8+/-20.3 pM; P=0.037. Endogenous somatostatin exerts a continuous restraint on histamine and gastrin release from the gastric mucosa and significantly reduces baseline acid secretion.
Fykse
Vidar
V
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway.
Coy
David H
DH
Waldum
Helge Lyder
HL
Sandvik
Arne Kristian
AK
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004702:Endocrine Glands / Q000187:drug effects*; D005088:Exocrine Glands / Q000187:drug effects*; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology / Q000502:physiology*
D005755:Gastrins; D006727:Hormone Antagonists; C121568:PRL 2903; D010456:Peptides, Cyclic; D010726:Phosphodiesterase Inhibitors; D017481:Receptors, Somatostatin; D013004:Somatostatin; D006632:Histamine; C093733:somatostatin receptor 2; D001839:Bombesin; D015056:1-Methyl-3-isobutylxanthine