TY - JOUR T1 - Differential Actions of Peripheral Corticotropin-Releasing Factor (CRF), Urocortin II, and Urocortin III on Gastric Emptying and Colonic Transit in Mice: Role of CRF Receptor Subtypes 1 and 2 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 611 LP - 617 DO - 10.1124/jpet.301.2.611 VL - 301 IS - 2 AU - Vicente Martı́nez AU - Lixin Wang AU - Jean E. Rivier AU - Wylie Vale AU - Yvette Taché Y1 - 2002/05/01 UR - http://jpet.aspetjournals.org/content/301/2/611.abstract N2 - Peripheral CRF inhibits gastric emptying and stimulates colonic motor function in rats. We investigated the role of CRF1and CRF2 receptors in i.p. CRF-induced alterations of gut transit in conscious mice using selective CRF1 and CRF2 ligands injected i.p. Gastric emptying 2 h after ingestion of a solid chow meal and colonic transit (time to expel a bead inserted into the distal colon) were determined simultaneously. Rat/human (r/h)CRF, which has CRF1 > CRF2binding affinity, decreased distal colonic transit time at lower doses (6–12 μg/kg) than those inhibiting gastric emptying (20–60 μg/kg). Ovine CRF, a preferential CRF1 receptor agonist (6–60 μg/kg), reduced significantly the colonic transit time without altering gastric emptying, whereas the selective CRF2receptor agonists mouse urocortin II (20–60 μg/kg) and urocortin III (120 μg/kg) inhibited significantly gastric emptying without modifying colonic transit. The CRF1/CRF2receptor antagonist, astressin (30–120 μg/kg), dose dependently prevented r/hCRF (20 μg/kg)-induced inhibition of gastric emptying and reduction of colonic transit time. The selective CRF1 receptor antagonists, NBI-27914 (C18H20Cl4N4C7H8O3S) and CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine) (5–30 mg/kg), dose dependently blocked r/hCRF action on the colon without influencing the gastric response, whereas the CRF2receptor antagonist, antisauvagine-30 (30–100 μg/kg), dose dependently abolished r/hCRF-induced delayed gastric emptying and had no effect on colonic response. These data show that i.p. r/hCRF-induced opposite actions on upper and lower gut transit in conscious mice are mediated by different CRF receptor subtypes: the activation of CRF1 receptors stimulates colonic propulsive activity, whereas activation of CRF2 receptors inhibits gastric emptying. The American Society for Pharmacology and Experimental Therapeutics ER -