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1 Department of Medicine, Division of Digestive Diseases, University of California, Los Angeles and VA Greater Los Angeles Healthcare System, CURE: Digestive Diseases Research Center and Center for Neurovisceral Sciences & Women's Health, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: ytache{at}mednet.ucla.edu.
We characterized the influence of the selective corticotropin-releasing factor 2 (CRF2) receptor agonist, urocortin 2 (Ucn 2), injected intracisternally (ic), on gastric emptying and its mechanism of action compared with ic CRF or urocortin (Ucn 1) in conscious rats. The methylcellulose phenol red solution was gavaged 20 min after peptide injection and gastric emptying measured 20 min later. The ic injection of Ucn 2 (0.1 and 1 µg) and Ucn 1 (1 µg) decreased gastric emptying to 37.8 ± 6.9%, 23.1 ± 8.6% and 21.6 ± 5.9%, respectively, compared with 58.4 ± 3.8% in ic vehicle. At lower doses, Ucn 2 (0.03 µg) and Ucn 1 (0.1 µg) had no effect. The CRF2 antagonist, astressin2-B (3 µg, ic), antagonized ic Ucn 2 (0.1 µg) and CRF (0.3 µg) -induced inhibition of gastric emptying. Vagotomy enhanced ic Ucn 2 (0.1 or 1 µg)-induced inhibition of gastric emptying compared to sham-operated group, while blocking ic CRF (1 µg) action (45.5 ± 8.4% vs. 9.7 ± 9.7%). Sympathetic blockade by bretylium prevented ic and intracerebroventricular Ucn 2-induced delayed gastric emptying, while not influencing intravenous Ucn 2-, ic CRF- and ic Ucn 1-induced inhibition of gastric emptying. Prazosin abolished ic Ucn 2 inhibitory effect, while yohimbine and propranolol did not. None of the pretreatment modified basal gastric emptying. These data indicate that ic Ucn 2 induced a central CRF2-mediated inhibition of gastric emptying involving sympathetic 
1-adrenergic mechanisms independent from the vagus contrasting with the vagal-dependent inhibitory actions of CRF and Ucn 1.
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