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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Restraint stress delays solid gastric emptying via a central CRF and peripheral sympathetic neuron in rats

Department of Surgery, Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham, North Carolina

Submitted 26 July 2004 ; accepted in final form 27 September 2004

Central corticotropin-releasing factor (CRF) delays gastric emptying through the autonomic nervous system. CRF plays an important role in mediating delayed gastric emptying induced by stress. However, it is not clear whether a sympathetic or parasympathetic pathway is involved in the mechanism of central CRF-induced inhibition of solid gastric emptying. The purpose of this study was to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is mediated via a central CRF and peripheral sympathetic pathways. Using male Sprague-Dawley rats, CRF was injected intracisternally with or without various adrenergic-blocking agents. To investigate whether central CRF-induced inhibition of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats underwent celiac ganglionectomy 1 wk before the gastric emptying study. After solid meal ingestion (90 min), gastric emptying was calculated. To investigate the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF type₂ receptor antagonist, astressin₂-B, was intracisternally administered. Rats were subjected to a restraint stress immediately after the feeding. Intracisternal injection of CRF (0.1–1.0 µg) dose-dependently inhibited solid gastric emptying. The inhibitory effect of CRF on solid gastric emptying was significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but not by phentolamine. Restraint stress significantly delayed solid gastric emptying, which was improved by astressin₂-B, guanethidine, and celiac ganglionectomy. Our research suggests that restraint stress inhibits solid gastric emptying via a central CRF type₂ receptor and peripheral sympathetic neural pathway in rats.

blood-brain barrier; guanethidine; celiac ganglionectomy; corticotropin-releasing factor

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