Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF(2).

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 microg) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.c. saline+RX-77368. 4. The CRF(1)/CRF(2) antagonist, astressin-B (60 microg, i.c.) completely blocked i.c. rUcn (3 microg, i.c.)-induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5. The selective CRF(2) antagonist, astressin(2)-B (30, 60 or 100 microg, i.c. ) dose-dependently prevented i.c. rUCn action while the CRF(1) antagonist, NBI-27914 did not. 6. In conscious rats, rUcn (0.6 or 1 microg, i.c.) inhibited gastric emptying of an ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by astressin(2)-B. 7. These data show that i.c. rUcn acts through CRF(2) receptors to inhibit central vagal gastric contractile response and postoprandial emptying.