Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats.
OBJECTIVE
Corticotropin-releasing factor (CRF) exerts its action through CRF receptors 1 and 2 (CRF-R1 and CRF-R2). CRF has preferential affinity for CRF-R1, whereas urocortin displays high affinity for both. We investigated changes in colonic motor function after intraperitoneal (IP) injection of CRF-related peptides.


METHODS
Colonic motility was recorded in vivo in conscious rats equipped with electrodes chronically implanted in the cecum and proximal colon or in vitro in distal colon; fecal output was monitored in naive rats.


RESULTS
Rat CRF, rat urocortin, and amphibian sauvagine (10 microg/kg, IP) induced a new pattern of cecocolonic myoelectric activity characterized by clustered spike bursts of long duration; the percentage of occurrence was highest after CRF. The rank order of potency to increase fecal pellet output after IP peptide injection (0.3-10 microg/kg, IP) was CRF > urocortin = sauvagine. The CRF-R1/R2 antagonist astressin (33 microg/kg, IP) and the CRF-R1 antagonist CP-154,526 (20 mg/kg, subcutaneously) inhibited IP CRF-induced changes in cecocolonic myoelectric activity and IP CRF- and water avoidance stress-induced fecal output. In vitro, CRF injected into the inferior mesenteric artery increased distal colonic myoelectric activity compared with saline injection.


CONCLUSIONS
These results demonstrate that CRF acts peripherally to stimulate colonic motility and that CRF-R1 is primarily involved in mediating IP CRF/urocortin- and water avoidance stress-induced colonic motor response.
Maillot
C
C
CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA. ytache@ucla.edu
Million
M
M
Wei
J Y
JY
Gauthier
A
A
Taché
Y
Y
D000818:Animals; D001362:Avoidance Learning; D003106:Colon / Q000187:drug effects / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D003672:Defecation / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D013312:Stress, Physiological / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D054832:Urocortins; D014867:Water; D000099052:CRF Receptor, Type 1
C101628:CP 154526; D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D014867:Water; C104416:astressin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone