Peripheral urocortin delays gastric emptying: role of CRF receptor 2.
Urocortin, a new mammalian member of the corticotropin-releasing factor (CRF) family has been proposed to be the endogenous ligand for CRF receptor 2 (CRF-R2). We studied the influence of intravenous urocortin on gastric emptying and the role of CRF-R2 in peptide action and postoperative gastric ileus in conscious rats. The intravenous doses of rat CRF and rat urocortin producing 50% inhibition of gastric emptying were 2.5 and 1.1 microgram/kg, respectively. At these intravenous doses, CRF and urocortin have their actions fully reversed by the CRF-R1/CRF-R2 antagonist astressin at antagonist/agonist ratios of 5:1 and 67:1, respectively. Astressin (12 microgram/kg iv) completely prevented abdominal surgery-induced 54% inhibition of gastric emptying 3 h after surgery while having no effect on basal gastric emptying. The selective nonpeptide CRF-R1 antagonists antalarmin (20 mg/kg ip) and NBI-27914 (400 microgram/kg iv) did not influence intravenous CRF-, urocortin- or surgery-induced gastric stasis. These results as well as earlier ones showing that alpha-helical CRF9-41 (a CRF-R2 more selective antagonist) partly prevented postoperative ileus indicate that peripheral CRF-R2 may be primarily involved in intravenous urocortin-, CRF-, and abdominal surgery-induced gastric stasis.
Nozu
T
T
CURE: Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, Department of Medicine, Los Angeles 90073,
Martinez
V
V
Rivier
J
J
Taché
Y
Y
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D007415:Intestinal Obstruction / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D054832:Urocortins
C101531:CRF receptor type 2; D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D054832:Urocortins; C103016:antalarmin; C104416:astressin; D003346:Corticotropin-Releasing Hormone