Corticotropin-releasing factor (CRF) receptor type 2 (CRF2) exists in both cardiomyocytes and neurocytes. The purpose of this research was to explore if chronic treatment with urocortin 2 (UCN2), a CRF2 receptor agonist, at different doses can improve prognosis and regulate the expression of CRF2 receptor and calcium handling proteins without any adverse effects on behavior in heart failure. Heart failure was established in Sprague-Dawley rats and was confirmed by echocardiography. Heart failure rats were injected intraperitoneally with UCN2 (5, 10, or 20 µg·kg−1·d−1) for 30 days. Survival rate, cardiac function, expressions of cardiac CRF2 receptor, RyR2, SERCA2, and hypothalamic and hippocampal c-FOS, CRF receptor type 1 (CRF1) and CRF2 receptor were determined. Behavior was evaluated by Morris Water-Maze and Open-Field tests. Results showed that chronic peripheral UCN2 treatment improved survival rate in a dose–response manner and increased cardiac function and expression of CRF2 receptor and SERCA2 in heart failure, especially at the high dosage. Moreover, cellular-fos (c-FOS), CRF1 receptor, and CRF2 receptor expressions of both hypothalamic and hippocampal tissues were significantly increased in high dosage group. Furthermore, the behavior tests suggested that chronic UCN2 treatment did not exacerbate stress/anxiety-like behavior in HF. In conclusion, chronic peripheral treatment with UCN2 increases survival in a dose–response manner in heart failure rats without inducing stress/anxiety-like behavior.

2018-02-01·Brain Research4区 · 医学

Anxiolytic- and antidepressant-like actions of Urocortin 2 and its fragments in mice

4区 · 医学

Article

作者: Pintér, Dávid ; Szabó, Gyula ; Csabafi, Krisztina ; Bagosi, Zsolt ; Bozsó, Zsolt ; Telegdy, Gyula ; Tóth, Gábor ; Szolomájer-Csikós, Orsolya ; Balangó, Beáta

The aim of the present study was to investigate the potential anxiolytic- and antidepressant-like actions of Urocortin 2 (Ucn2) and its two fragments, Ucn2 (1-21) and Ucn2 (22-38), in mice, in an attempt to identify the biologically active sequence of this 38 amino acid neuropeptide. In this purpose, male C57BL/6 mice were treated intracerebroventricularly (icv) with 0.125, 0.25, 0.5 and 1 µg/2 µl of Ucn2, Ucn2 (1-21) or Ucn2 (22-38). After 30 min, the mice were evaluated in an elevated plus-maze test and a forced swim test for anxiety- and depression-like behavior, respectively. Each test lasted 5 min. Ucn2 at dose of 0.25 µg/2 µl and Ucn2 (1-21) at dose of 0.125 µg/2 µl, but not Ucn2 (22-38), increased significantly the number of entries into and the time spent in the open-arms, without influencing the total number of entries. In parallel, the same doses of Ucn2 and Ucn2 (1-21), but not Ucn2 (22-38), increased significantly the climbing and the swimming activity, while decreasing significantly the time of immobility. In addition, Ucn2 at doses of 0.125 µg/2 µl and 0.5 µg/2 µl decreased significantly the time of immobility, but they did not change the other parameters. The present study demonstrates that Ucn2 exerts anxiolytic- and antidepressant-like effects in C57BL/6 mice, which are mediated by the N-terminal, but not the C-terminal fragment of the peptide. The establishment of the smallest active sequence by further fragmentation of Ucn2 (1-21) may allow the synthesis of new anxiolytic and antidepressant drugs.

2015-10-01·International Journal of Cardiology2区 · 医学

Urocortin 2 protects heart and kidney structure and function in an ovine model of acute decompensated heart failure: Comparison with dobutamine

2区 · 医学

Article

作者: Mark Richards, A ; Charles, Christopher J ; Ellmers, Leigh J ; Rademaker, Miriam T

BACKGROUNDRenal dysfunction is a frequent complication and crucial determinant of outcome in acute decompensated heart failure (ADHF). The aim of the study was to assess urocortin 2 (Ucn2) as a short-term therapy in ADHF with a focus on its renal effects. Comparison was made with dobutamine to distinguish effects beyond pure inotropism.METHODSSheep with ADHF received a 2-day infusion of a vehicle-control, Ucn2 or dobutamine (n=6/grp).RESULTSCompared to controls, Ucn2 and dobutamine produced matched improvements in cardiac contractility and output and arterial pressure, whereas reductions in central venous and left atrial pressures were greater with Ucn2. Both agents comparably repressed ADHF-activated hormone systems with the exception of the natriuretic peptides, which fell significantly during dobutamine but not Ucn2. While Ucn2 and dobutamine increased creatinine clearance and urine volume similarly, only Ucn2 induced a significant natriuresis. Ucn2 also decreased collagen deposition in the heart and kidney and suppressed gene expression of collagen-1, transforming growth factor-β1, components of the angiotensin system (angiotensinogen, angiotensin-converting enzyme, type-1 receptor) and markers of hypertrophy (GATA binding protein-4, β-myosin heavy chain), apoptosis (caspase3) and inflammation/injury (interleukin-18, cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1) in these tissues, while increasing cardiac natriuretic peptide mRNA. In contrast, dobutamine produced reduced or opposite effects on expression of these factors.CONCLUSIONSUcn2 administration in ADHF has favorable effects on hemodynamics, the natriuretic peptides and tissue mediators of inflammation, fibrosis, apoptosis and hypertrophy that stand in contrast to dobutamine. These data support Ucn2's potential as a renoprotective therapeutic in this setting.

100 项与 UCN2(Gubra) 相关的药物交易

登录后查看更多信息