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

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. 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. 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. The CRF 1 /CRF 2 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). The selective CRF 2 antagonist, astressin 2 ‐B (30, 60 or 100 μg, i.c.) dose‐dependently prevented i.c. rUCn action while the CRF 1 antagonist, NBI‐27914 did not. 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 astressin 2 ‐B. These data show that i.c. rUcn acts through CRF 2 receptors to inhibit central vagal gastric contractile response and postoprandial emptying. British Journal of Pharmacology (2002) 136 , 237–247; doi: 10.1038/sj.bjp.0704713