Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2 receptors.
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 (i.c.) 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 i.c. inhibited gastric emptying in a dose-dependent manner, with ED50 values of 0.31, 0.13, and 0.08 microgram/rat, respectively. Rat CRF-(6-33) (0.1-10 micrograms i.c.) had no effect. The nonselective CRF1 and CRF2 receptor antagonist, astressin, injected i.c. completely blocked the inhibitory effect of i.c. 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 i.c. 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.
Martinez
V
V
CURE: Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, University of California 90073, USA.
Barquist
E
E
Rivier
J
J
Taché
Y
Y
D029845:Amphibian Proteins; D000821:Animal Feed; D000818:Animals; D001921:Brain / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology*; D014579:Urotensins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D029845:Amphibian Proteins; D010446:Peptide Fragments; D036361:Peptide Hormones; D010455:Peptides; D018019:Receptors, Corticotropin-Releasing Hormone; D014579:Urotensins; C104416:astressin; C025727:sauvagine; D003346:Corticotropin-Releasing Hormone; C029676:urotensin I