CENTRAL CRF INHIBITS GASTRIC-EMPTYING OF A NUTRIENT SOLID MEAL IN RATS - THE ROLE OF CRF2 RECEPTORS

Corticotropin-releasing factor (CRF)-related peptides exhibit differen t 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 th e CRF receptor subtype involved. CRF, urotensin I (suckerfish), and sa uvagine (frog) injected IC inhibited gastric emptying in a dose-depend ent manner, with ED50 values of 0.31, 0.13, and 0.08 mu g/rat, respect ively. Rat CRF-(6-33) (0.1-10 mu g 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 wi th antagonist-to-agonist ratios of 3:1, 10:1, and 16:1, respectively. The CRF1-selective receptor antagonist NBI-27914 injected IC at a rati o of 170:1 had no effect. These data show that central CRF and CRF-rel ated peptides are potent inhibitors of gastric emptying of a solid mea l with a rank order of potency characteristic of the CRF2 receptor sub type affinity (sauvagine > urotensin I > CRF). In addition, the revers al by astressin but not by the CRF1-selective receptor antagonist furt her supports the view that the CRF2 receptor subtype is primarily invo lved in central CRF-induced delayed gastric emptying.