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 CRF1 or CRF2 receptors are helping to uncover the specific functions of CRF receptor subtypes. Central or peripheral CRF2 receptor activation suppresses feeding independently of CRF1 receptors. In the rat, central administration of CRF2 receptor agonists promotes satiation without eliciting the malaise, behavioral arousal or anxiogenesis associated with CRF, receptor agonists. Conversely, central administration of CRF1 receptor agonists elicits short-onset anorexia independently of CRF2 receptor activation. With respect to gastrointestinal motor function, stress inhibits gastric motility through CRF2 receptor-dependent central autonomic and peripheral myenteric systems. By contrast, stress stimulates colonic motility via CRF, 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.