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Am J Physiol Gastrointest Liver Physiol 274: G965-G970, 1998;
0193-1857/98 $5.00
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Vol. 274, Issue 5, G965-G970, May 1998

Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2 receptors

V. Martinez1, E. Barquist2, J. Rivier3, and Y. Taché1

1 CURE: Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center and Department of Medicine and Brain Research Institute, University of California, Los Angeles 90073; 3 Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92038; and 2 Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

Corticotropin-releasing factor (CRF)-related peptides exhibit different affinity for the receptor subtypes 1 and 2 cloned in the rat brain. We investigated, in conscious rats, the effects of intracisternal (IC) injection of CRF (rat/human) on the 5-h rate of gastric emptying of a solid nutrient meal (Purina chow and water ad libitum for 3 h) and the CRF receptor subtype involved. CRF, urotensin I (suckerfish), and sauvagine (frog) injected IC inhibited gastric emptying in a dose-dependent manner, with ED50 values of 0.31, 0.13, and 0.08 µg/rat, respectively. Rat CRF-(6---33) (0.1-10 µg ic) had no effect. The nonselective CRF1 and CRF2 receptor antagonist, astressin, injected IC completely blocked the inhibitory effect of IC CRF, urotensin I, and sauvagine with antagonist-to-agonist ratios of 3:1, 10:1, and 16:1, respectively. The CRF1-selective receptor antagonist NBI-27914 injected IC at a ratio of 170:1 had no effect. These data show that central CRF and CRF-related peptides are potent inhibitors of gastric emptying of a solid meal with a rank order of potency characteristic of the CRF2 receptor subtype affinity (sauvagine > urotensin I > CRF). In addition, the reversal by astressin but not by the CRF1-selective receptor antagonist further supports the view that the CRF2 receptor subtype is primarily involved in central CRF-induced delayed gastric emptying.

corticotropin-releasing factor; sauvagine; urotensin I; astressin; NBI-27914; CRF-(6---33); CRF antagonists; brain


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