Intravenous injection of urocortin 1 induces a CRF2 mediated increase in circulating ghrelin and glucose levels through distinct mechanisms in rats

Urocortins (Ucns) injected peripherally decrease food intake and gastric emptying through peripheral CRF2 receptors in rodents. However, whether Ucns influence circulating levels of the orexigenic and prokinetic hormone, ghrelin has been little investigated. We examined plasma levels of ghrelin and blood glucose after intravenous (iv) injection of Ucn 1, the CRF receptor subtype involved and underlying mechanisms in ad libitum fed rats equipped with a chronic iv cannula. Ucn 1 (10 μg/kg, iv) induced a rapid onset and long lasting increase in ghrelin levels reaching 68% and 219% at 0.5 and 3 h post injection respectively and a 5-h hyperglycemic response. The selective CRF2 agonist, Ucn 2 (3 μg/kg, iv) increased fasting acyl (3 h: 49%) and des-acyl ghrelin levels (3 h: 30%) compared to vehicle while the preferential CRF1 agonist, CRF (3 μg/kg, iv) had no effect. Ucn 1's stimulatory actions were blocked by the selective CRF2 antagonist, astressin2-B (100 μg/kg, iv). Hexamethonium (10 mg/kg, sc) prevented Ucn 1-induced rise in total ghrelin levels while not altering the hyperglycemic response. These data indicate that systemic injection of Ucns induces a CRF2-mediated increase in circulating ghrelin levels likely via indirect actions on gastric ghrelin cells that involves a nicotinic pathway independently from the hyperglycemic response.

► Intravenous urocortin 1 increases plasma total ghrelin and blood glucose in fed rats.
► Intravenous CRF2 receptor agonist, urocortin 2 increases fasted plasma acyl ghrelin levels.
► The increase in plasma ghrelin and glucose by urocortin 1 is CRF2 receptor mediated.
► Ghrelin but not glucose rise by urocortin 1 requires the integrity of autonomic transmission.