Urocortin II
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Urocortin 2 (Ucn2) is an endogenous peptide in the corticotrophin-releasing factor (CRF) family.[1]
Urocortin II is a 38-amino acid peptide that is a member of the CRF family of peptides. Unlike Urocortin I, Urocortin II is highly selective for the CRF2 receptor and does not show affinity for the CRF binding protein.
Receptor
Urocortin (UCN) II, also known as stresscopin-related peptide, is a 38 amino acid member of the mammalian corticotropin-releasing hormone (CRH) peptide family, which also includes CRH, UCN I, and UCN III.[1][2] CRH mainly binds to type 1 CRH receptors (CRH1), while UCN II and III bind primarily to type 2 CRH receptors, and UCN I binds to both (CRH2).[1][2] Each of these hormones has distinctive distribution patterns in the central nervous system and the periphery, suggesting each peptide may have distinct behavioral and physiological effects, although all have been associated with anxiety.[2][3][4][5] In general, agonism of CRH1 receptors is posited to be anxiogenic and agonism of CRH2 receptors is posited to be anxiolytic.[6]
Urocortin II has been shown to have anorexigenic effects and hypotensive effects similar to Urocortin, but does not induce secretion of ACTH.
The activation of cAMP/PKA by Ucn2 gives similar effects to the β-adrenergic pathway. Ucn2 increases left ventricular function independent of the β-adrenergic receptor but dependent on the binding of Ucn2 to CFR2.[6][7][8][9] Ucn2 is an agonist for the G-protein coupled CRF1 and CRF2 receptors. It is highly selective for CRF2 which is predominantly found in the myocardium, blood vessels and peripheral tissues. This association provides reason for its strong cardiovascular effects. When Ucn2 binds CRF2 it activates adenyl-cyclase to increase cAMP which activates PKA and results in the noted changes to cardiovascular function.[1]
The ability of Ucn2 to produce PKA and alter calcium flux has led to the hypothesis that administration of Ucn2 may increase the risk of arrhythmias.[7][8][9]