In vitro excitatory actions of corticotropin-releasing factor on rat colonic motility

Corticotropin-releasing factor (CRF) has been shown to affect gastrointestinal functions, however, a direct effect of CRF on the intestine has not been demonstrated. To determine the direct effect of CRF and its antagonist alpha-helical-CRF9-41 (alpha-h-CRF) on the enteric nervous system, we studied the action of these substances on electrical and mechanical parameters of peristaltic activity on isolated distal colon of the rat. The effects of CRF were evaluated in vitro on rat isolated colonic segments in which intraluminal pressure, longitudinal displacement, ejected fluid volume and extracellular electrical activity were simultaneously recorded during colonic peristaltic reflex. The addition of CRF (10(-10) - 10(-8) M) to the bath fluid provoked a concentration-dependent increase of both mechanical and electrical peristaltic activity. The CRF-receptor antagonist alpha-h-CRF dose-dependently (10(-10) - 10(-7) M) induced a decrease of the colonic mechanical and electrical activity and prevented (10(-8) - 10(-6) M) CRF (10(-8) M) maximal effects. These results indicate: (a) CRF can exert its effects on colon functions by a direct action, (b) a specific CRF-receptor is present in the rat colon. Indeed, CRF effects are antagonized by the specific CRF antagonist alpha-h-CRF, (c) the fact the alpha-h-CRF displays an activity on its own reveals that colonic functions are controlled by an endogenous CRF tonic activity.