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

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.e. with rUcn and 20 min later, with i.e. RX-77368. CRF antagonists were injected i.e. 10 min before rUcn. 3 RX-77368 (1.5, 3, 10, 30 and 100 ng, i.e.) 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.e. saline. Ucn (1, 3 or 10 mug) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.e. saline+RX-77368. 4 The CRF1/CRF2 antagonist, astressin-B (60 mug, i.e.) completely blocked i.e. rUcn (3 mug, i.e.)induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5 The selective CRF2 antagonist, astressin(2)-B (30, 60 or 100 mug, i.e.) dose-dependently prevented i.e. rUCn action while the CRF1 antagonist, NBI-27914 did not. 6 In conscious rats, rUcn (0.6 or 1 mug, i.e.) 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.e. rUcn acts through CRF2 receptors to inhibit central vagal gastric contractile response and postoprandial emptying.