Central somatostatin receptor 1 activation reverses acute stress-related alterations of gastric and colonic motor function in mice.

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, acts in the brain to inhibit stress-induced adrenocorticotropic hormone and epinephrine secretion. We investigated whether ODT8-duanyu1942 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-duanyu1942 (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 effect. The increased food intake was inhibited by i.c.v. sst(2) antagonist while the reduced FPO was unchanged. ODT8-duanyu1942 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-duanyu1942 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. © 2011 Blackwell Publishing Ltd.

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