Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: Role of CRF2

Abstract

1. Corticotropin-releasing factor (CRF) acts in the brain to inhibit thyrotropin-releasing hormone (TRH) analogue, RX-77368-induced vagal stimulation of gastric motility. We investigated CRF receptor-mediated actions of rat urocortin (rUcn) injected intracisternally (ic) on gastric motor function. 2. Urethane-anaesthetized rats with strain gauges on the gastric corpus were injected i.c. with rUcn and 20 min later, with i.c. RX-77368. CRF antagonists were injected i.c. 10 min before rUcn. 3. RX-77368 (1.5, 3, 10, 30 and 100 ng, i.c.) dose-dependently increased corpus contractions, expressed as total area under the curve (AUC, mV min-1) to 2.6 ± 2.5, 6.1 ± 5.9, 9.8 ± 2.6, 69.7 ± 21.7 and 74.9 ± 28.7 respectively vs 0.2 ± 0.1 after i.c. saline. Ucn (1, 3 or 10 μg) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.c. saline + RX-77368. 4. The CRF1/CRF2 antagonist, astressin-B (60 μg, i.c.) completely blocked i.c. rUcn (3 μg, i.c.)-induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5. The selective CRF2 antagonist, astressin2-B (30, 60 or 100 μg, i.c.) dose-dependently prevented i.c. rUCn action while the CRF1 antagonist, NBI-27914 did not. 6. In conscious rats, rUcn (0.6 or 1 μg, i.c.) inhibited gastric emptying of an ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by astressin2-B. 7. These data show that i.c. rUcn acts through CRF2 receptors to inhibit central vagal gastric contractile response and postoprandial emptying.