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NEUROREGULATION AND MOTILITY

Urocortin 2 acts centrally to delay gastric emptying through sympathetic pathways while CRF and urocortin 1 inhibitory actions are vagal dependent in rats

CURE/Digestive Diseases Research Center and Center for Neurovisceral Sciences and Women’s Health, Division of Digestive Diseases, Department of Medicine, University of California and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California

We characterized the influence of the selective corticotropin-releasing factor 2 (CRF₂) receptor agonist human urocortin 2 (Ucn 2), injected intracisternally, on gastric emptying and its mechanism of action compared with intracisternal CRF or urocortin (Ucn 1) in conscious rats. The methylcellulose phenol red solution was gavaged 20 min after peptide injection, and gastric emptying was measured 20 min later. The intracisternal 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% after intracisternal 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 intracisternal Ucn 2 (0.1 µg) and CRF (0.3 µg)-induced inhibition of gastric emptying. Vagotomy enhanced intracisternal Ucn 2 (0.1 or 1 µg)-induced inhibition of gastric emptying compared with sham-operated group, whereas it blocked intracisternal CRF (1 µg) inhibitory action (45.5 ± 8.4% vs. 9.7 ± 9.7%). Sympathetic blockade by bretylium prevented intracisternal and intracerebroventricular Ucn 2-induced delayed gastric emptying, whereas it did not influence intravenous Ucn 2-, intracisternal CRF-, and intracisternal Ucn 1-induced inhibition of gastric emptying. Prazosin abolished the intracisternal Ucn 2 inhibitory effect, whereas yohimbine and propranolol did not. None of the pretreatments modified basal gastric emptying. These data indicate that intracisternal 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.

adrenergic receptors; vagus; corticotropin-releasing hormone receptor

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