Central Somatostatin Receptor 1 Activation Reverses Acute Stress-related Alterations of Gastric and Colonic Motor Function in Mice

Overview

Journal Neurogastroenterol Motil

Specialties Gastroenterology
Neurology

Date 2011 May 14

PMID 21564422

Citations 12

Authors

A Stengel

M Goebel-Stengel

L Wang

M Larauche

J Rivier

Y Tache

Affiliations

Soon will be listed here.

Abstract

Background: Corticotropin-releasing factor (CRF) signaling induced by stress is well established to delay gastric emptying (GE) and stimulate colonic functions. The somatostatin receptor (sst(1-5) ) agonist, ODT8-SST acts in the brain to inhibit stress-induced adrenocorticotropic hormone and epinephrine secretion. We investigated whether ODT8-SST acts in the brain to influence stress-related alterations of gastric and colonic motor function and sst receptor subtype(s) involved.

Methods: Peptides were injected intracerebroventricularly (i.c.v.) under short isoflurane anesthesia and GE, fecal pellet output (FPO) and distal colonic motility monitored in conscious mice.

Key Results: The stress of acute anesthesia/vehicle i.c.v. injection reduced GE by 67% and increased defecation by 99% compared to non-injected controls. Both responses were abolished by ODT8-SST (1μg= 0.75nmol) or sst(1) agonist (0.65-1.95nmol). The sst(1) agonist (1.95nmol) also prevented the abdominal surgery-induced delayed GE. Octreotide (sst(2) >sst(5) > sst(3) ) and the sst(2) or sst(4) agonists (1μg=0.78 or 0.70nmol, respectively) injected i.c.v. did not influence FPO while i.c.v. somatostatin-28 mimicked ODT8-SST's effect. The ODT8-SST-induced increased food intake was inhibited by i.c.v. sst(2) antagonist while the reduced FPO was unchanged. ODT8-SST i.c.v. reduced distal colonic motility in semi-restrained mice compared with vehicle and blocked water avoidance- and i.c.v. CRF (0.5μg=0.09nmol)-induced stimulated FPO while a similar colonic secretomotor response to i.p. 5-hydroxytryptophane (10mgkg(-1) =36.4μmol kg(-1) ) was unaltered. Conclusions & Inferences ODT8-SST counteracts stress/i.c.v. CRF-related stimulation of colonic motor function and delayed GE which can be reproduced mainly by activation of sst(1) receptors. These data opens new insight to brain somatostatinergic signaling pathways interfering with brain circuitries involved in gut motor responses to acute stress.

Citing Articles

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity.

Kumar U, Singh S Int J Mol Sci. 2020; 21(7).

PMID: 32272767 PMC: 7177963. DOI: 10.3390/ijms21072568.

Central somatostatin signaling and regulation of food intake.

Stengel A, Tache Y Ann N Y Acad Sci. 2019; 1455(1):98-104.

PMID: 31237362 PMC: 6834873. DOI: 10.1111/nyas.14178.

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.

Gunther T, Tulipano G, Dournaud P, Bousquet C, Csaba Z, Kreienkamp H Pharmacol Rev. 2018; 70(4):763-835.

PMID: 30232095 PMC: 6148080. DOI: 10.1124/pr.117.015388.

Colonic Transit Time and Gut Peptides in Adult Patients with Slow and Normal Colonic Transit Constipation.

Riezzo G, Chimienti G, Clemente C, DAttoma B, Orlando A, Rinaldi C Biomed Res Int. 2017; 2017:3178263.

PMID: 29082242 PMC: 5610809. DOI: 10.1155/2017/3178263.

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response.

Stengel A, Tache Y Front Neurosci. 2017; 11:231.

PMID: 28487631 PMC: 5403923. DOI: 10.3389/fnins.2017.00231.

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