Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats

The CRF receptor subtype mediating the colonic and gastric motor responses to central CRF was investigated in conscious rats. CRF (0.6 mug/rat) injected intracerebroventicularly (i.c.v.) or 1 h water avoidance stress stimulated defecation (pellet/60 min: 4.1 +/- 1.0 and 8.7 +/- 0.7 respectively vs. 0.3 +/- 0.3 in i.c.v. vehicle/no stress). The CRF receptor 1 (CRF-RI) antagonist, NBI-27914 (50-100 mug/rat) injected i.c.v., abolished the colonic response to i.c.v. CRF and dose-dependently reduced that induced by water avoidance stress. NBI-27914 (100 mug/rat) injected peripherally did not influence the defecatory response to stress. The peptide CRF-R1/R2 antagonist, astressin (10 mug/rat, i.c.v.) inhibited the colonic motor response to i.c.v. CRF and stress similarly as NBI-27914 injected i.c.v. at 100 mug/rat. Intracisternal (i.c.) injection of astressin (10 mug/rat) also completely prevented CRF (0.6 g, i.c.)-induced delayed gastric emptying while i.c. NBI-27914 (50 or 100 mug) had no effect. These results indicate a differential role of central CRF receptor subtypes in the colonic stimulatory and gastric inhibitory motor responses to central CRF and that the CRF component of stress-related activation of colonic expulsion is primarily mediated by CRF-R1. (C) 2001 Elsevier Science B.V. All rights reserved.