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 microg/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-R1) antagonist, NBI-27914 (50-100 microg/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 microg/rat) injected peripherally did not influence the defecatory response to stress. The peptide CRF-R1/R2 antagonist, astressin (10 microg/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 microg/rat. Intracisternal (i.c.) injection of astressin (10 microg/rat) also completely prevented CRF (0.6 g, i.c.)-induced delayed gastric emptying while i.c. NBI-27914 (50 or 100 microg) 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.
CURE: Digestive Diseases Research Center, Veterans Administration Greater Los Angeles Healthcare System, Department of Medicine, Digestive Disease Division and Brain Research Institute, University of California at Los Angeles, Los Angeles, CA 90073,USA.
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D000818:Animals; D002946:Cisterna Magna / Q000187:drug effects; D003106:Colon / Q000294:innervation / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D003672:Defecation / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006727:Hormone Antagonists / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013312:Stress, Physiological; D000099052:CRF Receptor, Type 1
D006727:Hormone Antagonists; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C104416:astressin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone