Nibbling at CRF receptor control of feeding and gastrocolonic motility.
Inadequate pharmacological tools, until recently, hindered the understanding of the roles of corticotropin-releasing factor (CRF) receptor subtypes in appetite regulation and gastrocolonic motor function. Now, novel ligands that are selective for CRF(1) or CRF(2) receptors are helping to uncover the specific functions of CRF receptor subtypes. Central or peripheral CRF(2) receptor activation suppresses feeding independently of CRF(1) receptors. In the rat, central administration of CRF(2) receptor agonists promotes satiation without eliciting the malaise, behavioral arousal or anxiogenesis associated with CRF(1) receptor agonists. Conversely, central administration of CRF(1) receptor agonists elicits short-onset anorexia independently of CRF(2) receptor activation. With respect to gastrointestinal motor function, stress inhibits gastric motility through CRF(2) receptor-dependent central autonomic and peripheral myenteric systems. By contrast, stress stimulates colonic motility via CRF(1) receptor-dependent sacral parasympathetic and colonic myenteric mechanisms. These findings have important physiological implications and suggest targeted approaches for the pharmacotherapy of obesity and stress-related functional gastrointestinal and eating disorders.
Zorrilla
Eric P
EP
Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ezorrilla@scripps.edu
Taché
Yvette
Y
Koob
George F
GF
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D003106:Colon / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000502:physiology; D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D012527:Satiation / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology
C101531:CRF receptor type 2; D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone