Urocortins and the regulation of gastrointestinal motor function and visceral pain.
Urocortin (Ucn) 1, 2 and 3 are corticotropin-releasing factor (CRF)-related peptides recently characterized in mammals. Urocortin 1 binds with high affinity to CRF type 1 (CRF1) and type 2 (CRF2) receptors while Ucn 2 and Ucn 3 are selective CRF2 ligands. They also have a distinct pattern of distribution, both in the brain and the gastrointestinal tract, compatible with a role mediating, with CRF, the response to stress. In rats and mice, Ucn 1 injected centrally or peripherally inhibited gastric emptying and stimulated colonic propulsive motor function, mimicking the effects of stress or exogenous CRF. Centrally administered Ucn 2 inhibited gastric emptying with similar potency as CRF, while Ucn 1 and Ucn 3 were less potent. However, after peripheral administration, Ucn 1 and Ucn 2 were more potent than CRF. In mice, centrally administered Ucn 1 and 2 stimulated colonic motility with lower potency than CRF, and Ucn 3 was inactive. Studies with selective CRF1 and CRF2 antagonists demonstrated that the gastric-inhibitory and colonic-stimulatory effects of exogenously administered Ucns are mediated through CRF2 and CRF1 receptors, respectively. In addition, Ucn 2 showed visceral anti-nociceptive activity associated with the selective activation of CRF2 receptors. These observations suggest that, acting centrally and peripherally, Ucns might play a significant role in the modulation of gastrointestinal motor and pain responses during stress and stress-related pathophysiological conditions.
Department of Medicine, CURE/Digestive Diseases Research Center, Center for Neurovisceral Sciences and Women's Health, University of California, Los Angeles, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Vicente
V
Martinez
Lixin
L
Wang
Mulugeta
M
Million
Jean
J
Rivier
Yvette
Y
Taché
D000818:Animals; D003106:Colon / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004068:Digestive System Physiological Phenomena; D005399:Fishes; D005769:Gastrointestinal Motility / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D010146:Pain; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology; D054832:Urocortins; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone