The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Wylie Vale - One of the best experts on this subject based on the ideXlab platform.
-
Corticotropin-Releasing Hormone Receptor Signaling
Reference Module in Neuroscience and Biobehavioral Psychology, 2017Co-Authors: Bhawanjit K. Brar, Marilyn H. Perrin, Wylie ValeAbstract:The primary response to a stressful event is activation of the hypothalamic–pituitary–adrenal axis. The stress response results in the synthesis and release of corticotropin-releasing hormone (CRH) from the hypothalamus, followed by an increased release of proopiomelanocortin peptides (adrenocorticotropic hormone, melanocyte-stimulating hormones, and endorphins) from the pituitary gland. Adrenocorticotropic hormone (ACTH) acts on the adrenal gland to cause release of glucocorticoids. The initial isolation of CRH, a 41-amino acid peptide, was based on its function as the major secretagogue of ACTH. Three more mammalian CRH-related ligands, Urocortin (Ucn), Urocortin II (Ucn 2), and Urocortin III (Ucn 3), have now been cloned. The importance of the CRH system as a major integrator of behavioral, autonomic and endocrine responses to stress is underscored by its effects on learning and memory, Alzheimer's and Parkinson disease, appetite and weight control, addiction, cancer and a possible role in affective disorders such as melancholic depression. The diverse functions of the CRH peptides in physiology and disease is attributed to the downstream signaling pathways they modulate in a diverse number of cell types and tissues and disease states.
-
mediated action on gastric transit
2016Co-Authors: Mulugeta Million, Jean Rivier, Celine Maillot, Paul Saunders, Wylie ValeAbstract:Human Urocortin II, a novel CRF-related peptide, displays a selective CRF2 recepto
-
Human endometrium expresses Urocortin II and III messenger RNA and peptides.
Fertility and sterility, 2006Co-Authors: Pasquale Florio, Wylie Vale, Paulo B. Torres, Michela Torricelli, Paolo Toti, Felice PetragliaAbstract:Urocortin II and Urocortin III are recently identified corticotropin-releasing factor–related neuropeptides, and their endometrial expression throughout the menstrual cycle and in early pregnancy was evaluated in the present study by semiquantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. The endometrial expression of Urocortin II mRNA was significantly ( P P
-
The cardiovascular physiologic actions of Urocortin II: acute effects in murine heart failure.
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Tracy L. Bale, Wylie Vale, Jean Rivier, Masahiko Hoshijima, Nancy D. Dalton, Keith R. Anderson, Kuo-fen Lee, Kenneth R. Chien, Kirk L. PetersonAbstract:Corticotropin-releasing factor (CRF) and its paralogues Urocortin (Ucn)I, -II, and -III signal by activating their receptors, CRF receptors (CRFR)1 and -2, to maintain homeostasis through endocrine, autonomic, and behavioral responses. CRFR2 is found in cardiomyocytes and in endothelial and smooth muscle cells of the systemic vasculature. Echocardiography and cardiac catheterization were used in mice to assess the physiologic effects of i.v. UcnII and CRFR2 deficiency on left ventricular function and the systemic vasculature. UcnII treatment augmented heart rate, exhibited potent inotropic and lusitropic actions on the left ventricle, and induced a downward shift of the diastolic pressure-volume relation. UcnII also reduced systemic arterial pressure, associated with a lowering of systemic arterial elastance (end-systolic pressure/stroke volume) and systemic vascular resistance. CRFR2-deficient mice showed no alteration in cardiac contractility or blood pressure in response to UcnII administration, suggesting that the effects of UcnII are specific to CRFR2 function. Pretreatment with a β-adrenergic receptor antagonist, esmalol, had no effect on the inotropic or lusitropic effects of UcnII in vivo, indicating that its actions are independent of β-adrenergic receptors. Single i.v. bolus administration of UcnII to a heart failure model (muscle-specific LIM protein-deficient mice) produced significant enhancement of inotropic and lusitropic effects on left ventricular function and improved cardiac output. These results demonstrate the potent cardiovascular physiologic actions of UcnII in both wild-type and cardiomyopathic mice and support a potential beneficial use of this peptide in therapy of congestive heart failure.
-
Selective Activation of Corticotropin-Releasing Factor-2 Receptors on Neurochemically Identified Neurons in the Rat Dorsal Raphe Nucleus Reveals Dual Actions
The Journal of Neuroscience, 2004Co-Authors: Luise Pernar, Andre L. Curtis, Wylie Vale, Jean Rivier, Rita J ValentinoAbstract:The dorsal raphe (DR)-serotonin (5-HT) system has been implicated in stress-related psychiatric disorders. Stress may impact on this system through corticotropin-releasing factor (CRF), which densely innervates the DR. CRF binds to CRF-R1 and CRF-R2 receptors in the DR and has complex and opposing effects depending on the dose used and the endpoint examined. To clarify the impact of CRF on the DR-5-HT system, the effects of selectively activating CRF-R2 receptors (the predominant subtype) on extracellular DR neuronal activity were examined in halothane-anesthetized rats. Because the DR is neurochemically heterogeneous, when possible, neurons were labeled with neurobiotin for subsequent neurochemical classification as 5-HT or non-5-HT. Relatively low doses of Urocortin II (UII) (0.1-10 ng) injected into the DR inhibited most (79%; n = 34) neurons, whereas a higher dose (30 ng) inhibited 28% and activated 41% (n = 29). An analysis of effects on neurochemically identified neurons revealed that 5-HT neurons were inhibited by 0.1-10 ng of UII and activated by 30 ng of UII. Activation of 5-HT neurons by 30 ng of UII likely resulted from disinhibition because the majority of non-5-HT neurons were inhibited by this dose. Antisauvagine-30, but not antalarmin, antagonized UII, implicating CRF-R2 receptors in the effects. The results suggest that activation of CRF-R2 on DR-5-HT neurons inhibits neuronal activity, whereas activation of CRF-R2 receptors on non-5-HT neurons may indirectly excite DR-5-HT neurons through disinhibition. Importantly, the tone of the DR-5-HT system can be regulated in a dynamic manner through CRF-R2 activation, being either decreased or increased depending on the level of endogenous or exogenous ligand.
Gyula Telegdy - One of the best experts on this subject based on the ideXlab platform.
-
The interaction of Urocortin II and Urocortin III with amygdalar and hypothalamic cotricotropin-releasing factor (CRF) - reflections on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis
Neuropeptides, 2013Co-Authors: Zsolt Bagosi, Krisztina Csabafi, Miklos Palotai, Miklós Jászberényi, Imre Földesi, János Gardi, Gyula Szabó, Gyula TelegdyAbstract:Urocortin II (Ucn II) and Urocortin III (Ucn III) are selective agonists of the CRF receptor type 2 (CRFR2). The aim of the present experiments was to investigate the effects of Ucn II and Ucn III on the central CRF and peripheral glucocorticoids in rats. Increasing doses (0.5-1-2-5 μg/2 μl) of Ucn II or Ucn III were administered intracerebroventricularly, then CRF concentration was determined by immunoassays in two different brain regions, the amygdala and the hypothalamus, and in two different time paradigms, 5 and 30 min after the administration of peptides. In parallel with the second determination, plasma corticosterone concentration was measured by chemofluorescent assay. The amygdalar CRF amount was increased significantly by 0.5 and 5 μg of UCN II and 2 and 5 μg of UCN III in the 5 min experiments and by 5 μg of UCN II and 0.5 and 5 μg of UCN III in the 30 min experiments. The hypothalamic CRF content was not affected considerably in the 5 min paradigm, but it was influenced significantly in the 30 min paradigm, with 0.5 and 1 μg of UCN II and 0.5-2 μg of UCN III decreasing, and 2 and 5 μg of UCN II and 5 μg of UCN III increasing the hormone concentration, respectively. The plasma corticosterone concentration was decreased by 1 and 2 μg of UCN II and UCN III and increased by 0.5 and 5 μg of UCN III. The present results demonstrate that central administration of Ucn II and Ucn III modulate time-dependently and dose-dependently the amygdalar and the hypothalamic CRF concentration, and, directly or indirectly, the plasma corticosterone concentration. The present experiments suggest that the role of CRFR2 in the regulation of the HPA axis can be inhibitory or stimulatory, depending on the actual concentration of their agonists.
-
The effects of corticoptropin-releasing factor and the Urocortins on striatal dopamine release induced by electrical stimulation - An in vitro superfusion study
Neurochemical research, 2006Co-Authors: Zsolt Bagosi, Miklós Jászberényi, E. Bujdosó, Gyula TelegdyAbstract:The members of the CRF peptide family, corticotropin-releasing factor (CRF), Urocortin I (Ucn I), Urocortin II (Ucn II) and Urocortin III (Ucn III) coordinate endocrine and behavioral responses to stress. CRF has also been demonstrated to stimulate dopamine (DA) synthesis.
-
The Effects of Corticoptropin-Releasing Factor and the Urocortins on Striatal Dopamine Release Induced by Electrical Stimulation—An in vitro Superfusion Study
Neurochemical Research, 2006Co-Authors: Zsolt Bagosi, Miklós Jászberényi, E. Bujdosó, Gyula TelegdyAbstract:The members of the CRF peptide family, corticotropin-releasing factor (CRF), Urocortin I (Ucn I), Urocortin II (Ucn II) and Urocortin III (Ucn III) coordinate endocrine and behavioral responses to stress. CRF has also been demonstrated to stimulate dopamine (DA) synthesis. In our study, a superfusion system was used to investigate the effects of this peptide family on striatal DA release following electrical stimulation. The involvement of the CRF receptors was studied by pretreatment of rat striatal slices with selective CRF antagonists. CRF and Ucn I increased the release of [^3H]DA while Ucn II and Ucn III were ineffective. The CRFR1 antagonist antalarmin inhibited the [^3H]DA release induced by electrical stimulation and enhanced by CRF and Ucn I. The CRFR2 antagonist astressin-2B was ineffective. These results suggest that CRF and Ucn I mediate DA release through the activation of CRFR1. Ucn II and Ucn III are not involved in this process.
Stefanie Walther - One of the best experts on this subject based on the ideXlab platform.
-
nfat transcription factor regulation by Urocortin II in cardiac myocytes and heart failure
American Journal of Physiology-heart and Circulatory Physiology, 2014Co-Authors: Stefanie Walther, Sawsan Awad, Vassyl A Lonchyna, Lothar A. BlatterAbstract:Urocortin II (UcnII), a cardioactive peptide with beneficial effects in normal and failing hearts, is also arrhythmogenic and prohypertrophic. We demonstrated that cardiac effects are mediated by a phosphatidylinositol-3 kinase (PI3K)/Akt kinase (Akt)/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathways. Nuclear factor of activated T-cells (NFAT) transcription factors play a key role in the regulation of gene expression in cardiac development, maintenance of an adult differentiated cardiac phenotype, and remodeling processes in cardiac hypertrophy and heart failure (HF). We tested the hypothesis that UcnII differentially regulates NFAT activity in cardiac myocytes from both normal and failing hearts through the PI3K/Akt/eNOS/NO pathway. Isoforms NFATc1 and NFATc3 revealed different basal subcellular distribution in normal and HF rabbit ventricular myocytes with a nuclear NFATc1 and a cytosolic localization of NFATc3. However, in HF, the nuclear localization of NFATc1 was less pronounced, whereas the nuclear occupancy of NFATc3 was increased. In normal myocytes, UcnII induced nuclear export of NFATc1 and attenuated NFAT-dependent transcriptional activity but did not affect the distribution of NFATc3. In HF UcnII facilitated nuclear export of both isoforms and reduced transcriptional activity. NFAT regulation was mediated by a PI3K/Akt/eNOS/NO signaling cascade that converged on the activation of several kinases, including glycogen synthase kinase-3β (GSK3β), c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated kinase (p38), and PKG, resulting in phosphorylation, deactivation, and nuclear export of NFAT. In conclusion, while NFATc1 and NFATc3 reveal distinct subcellular distribution patterns, both are regulated by the UcnII-PI3K/Akt/eNOS/NO pathway that converges on the activation of NFAT kinases and NFAT inactivation. The data reconcile cardioprotective and prohypertrophic UcnII effects mediated by different NFAT isoforms.
-
Urocortin II regulates nfat transcription factor in adult rabbit cardiac myocytes
Biophysical Journal, 2012Co-Authors: Stefanie Walther, Lothar A. BlatterAbstract:Nuclear factor of activated T cells (NFAT) transcription factors play a key role during cellular remodelling associated with hypertrophy and heart failure (HF). We tested the hypothesis that the cardioprotective peptide Urocortin II (UcnII) regulates translocation and activation of NFAT.Rabbit ventricular myocytes were infected with recombinant adenoviruses encoding for NFAT-GFP fusion proteins (isoforms NFATc1 and NFATc3). The subcellular distribution of NFAT was quantified as the ratio of NFATnuc to NFATcyt fluorescence (RNFAT) and nuclear-cytosolic NFAT translocation was expressed as changes of RNFAT. Under basal unstimulated conditions NFATc3 was predominantly localized in the cytoplasm, whereas NFATc1 displayed a nuclear localization. UcnII (100 nM) caused NFATc1 export to the cytoplasm (RNFAT decreased from 2.25 to 1.03 after 24 hrs). UcnII did not affect nuclear-cytosolic NFATc3 distribution.UcnII-induced NFATc1 export to the cytoplasm was significantly (P<0.05) reduced (by 58-79%) by inhibition of guanylate cyclase (ODQ, 10 μM), calcineurin (Cyclosporin A, 1 μM), and GSK3s (Alsterpaullone, 1 μM). Inhibition of PI3K (Wortmannin, 300 nM) and nuclear transport protein crm1 (Leptomycin B, 40 nM) prevented the redistribution of NFATc1 to the cytoplasm completely.In ventricular myocytes from failing rabbit hearts, nuclear localization of NFATc3 was significantly enhanced compared to normal myocytes (RNFAT 0.78 vs. 0.58). Stimulation of HF myocytes with UcnII resulted in a translocation of NFATc3 back to the cytoplasm (RNFAT=0.56). In HF myocytes the nuclear localization of NFATc1 was less pronounced compared to normal myocytes (RNFAT: 1.97 in HF vs. 2.86 in normal ventricular cells). UcnII induced a further redistribution of NFATc1 out of the nucleus (RNFAT=0.97).We conclude that UcnII enhances the export of NFAT from the nucleus to the cytoplasm in ventricular myocytes involving the PI3K/cGMP/PKG/calcineurin- and PI3K/Akt/GSK3s-pathways and could thus positively affect remodeling in hypertrophy and HF.
-
Urocortin II Regulates NFAT Transcription Factor in Adult Rabbit Cardiac Myocytes
Biophysical Journal, 2012Co-Authors: Stefanie Walther, Lothar A. BlatterAbstract:Nuclear factor of activated T cells (NFAT) transcription factors play a key role during cellular remodelling associated with hypertrophy and heart failure (HF). We tested the hypothesis that the cardioprotective peptide Urocortin II (UcnII) regulates translocation and activation of NFAT.Rabbit ventricular myocytes were infected with recombinant adenoviruses encoding for NFAT-GFP fusion proteins (isoforms NFATc1 and NFATc3). The subcellular distribution of NFAT was quantified as the ratio of NFATnuc to NFATcyt fluorescence (RNFAT) and nuclear-cytosolic NFAT translocation was expressed as changes of RNFAT. Under basal unstimulated conditions NFATc3 was predominantly localized in the cytoplasm, whereas NFATc1 displayed a nuclear localization. UcnII (100 nM) caused NFATc1 export to the cytoplasm (RNFAT decreased from 2.25 to 1.03 after 24 hrs). UcnII did not affect nuclear-cytosolic NFATc3 distribution.UcnII-induced NFATc1 export to the cytoplasm was significantly (P
-
Urocortin II causes phosphorylation of enos and stimulation of no production in cardiac myocytes
Biophysical Journal, 2011Co-Authors: Stefanie Walther, Joachim Spiess, Li-zhen Yang, Burkert Pieske, Susanne Renz, Jens KockskämperAbstract:AIM: Urocortin II (UcnII) exerts beneficial effects in heart failure. In cardiac myocytes, UcnII exerts positive inotropic and lusitropic effects through a PKA-dependent pathway. We tested the hypothesis that, in addition, UcnII stimulates endothelial NO synthase (eNOS) and evaluated the underlying signaling pathways and mechanisms.METHODS: UcnII-induced phosphorylation of Akt and eNOS was measured using phospho-specific antibodies. Isolated cardiac myocytes were loaded with 5x10-6M DAF-FM and UcnII-induced changes in NO production were assessed by changes in DAF-FM fluorescence in electrically paced myocytes (0.5 Hz, room temperature) by means of confocal microscopy.RESULTS: In rabbit ventricular myocytes, UcnII caused increases in phosphorylation of Akt at Ser473 (+89.4±21.4%) and Thr308 (+60.4±39.7%) and phosphorylation of eNOS at Ser1177 (+49.6±25.9%; n=6-11, all P<0.05 vs untreated controls). Wortmannin (300nM) and LY294002 (10-5M), inhibitors of PI3K, largely reduced UcnII-induced phosphorylation of Akt and eNOS, respectively (n=11-20, P<0.05). Cellular NO production increased by 41.1±5.5% (n=20, P<0.01), which was inhibited by eNOS inhibitors, L-NIO (10-5M) and L-NAME (1mM) by ∼30% (n=4-8, P<0.05). Inhibition of PKA by H89 (5x10-6M) also reduced eNOS phosphorylation (n=11, P<0.05) but did not affect Akt phosphorylation. Direct stimulation of cAMP/PKA signaling via forskolin (10-5M) increased phosphorylation of eNOS (n=5, P<0.05) but not of Akt. When both PI3K/Akt (LY294002 10-5M) and cAMP/PKA (H89 10-6M) signaling were inhibited, the UcnII-induced increase of [NO]i was attenuated by ∼20% (n=10, P<0.01). UcnII also increased [NO]i in mouse, rat, and human ventricular myocytes as well as in rabbit atrial myocytes (n=4-12).SUMMARY: We conclude that, in cardiac myocytes, UcnII causes eNOS phosphorylation to stimulate cellular NO production via both cAMP/PKA and PI3K/Akt signaling.
-
Urocortin II Causes Phosphorylation of eNOS and Stimulation of NO Production in Cardiac Myocytes
Biophysical Journal, 2011Co-Authors: Stefanie Walther, Joachim Spiess, Li-zhen Yang, Burkert Pieske, Susanne Renz, Jens KockskämperAbstract:AIM: Urocortin II (UcnII) exerts beneficial effects in heart failure. In cardiac myocytes, UcnII exerts positive inotropic and lusitropic effects through a PKA-dependent pathway. We tested the hypothesis that, in addition, UcnII stimulates endothelial NO synthase (eNOS) and evaluated the underlying signaling pathways and mechanisms.METHODS: UcnII-induced phosphorylation of Akt and eNOS was measured using phospho-specific antibodies. Isolated cardiac myocytes were loaded with 5x10-6M DAF-FM and UcnII-induced changes in NO production were assessed by changes in DAF-FM fluorescence in electrically paced myocytes (0.5 Hz, room temperature) by means of confocal microscopy.RESULTS: In rabbit ventricular myocytes, UcnII caused increases in phosphorylation of Akt at Ser473 (+89.4±21.4%) and Thr308 (+60.4±39.7%) and phosphorylation of eNOS at Ser1177 (+49.6±25.9%; n=6-11, all P
Lothar A. Blatter - One of the best experts on this subject based on the ideXlab platform.
-
nfat transcription factor regulation by Urocortin II in cardiac myocytes and heart failure
American Journal of Physiology-heart and Circulatory Physiology, 2014Co-Authors: Stefanie Walther, Sawsan Awad, Vassyl A Lonchyna, Lothar A. BlatterAbstract:Urocortin II (UcnII), a cardioactive peptide with beneficial effects in normal and failing hearts, is also arrhythmogenic and prohypertrophic. We demonstrated that cardiac effects are mediated by a phosphatidylinositol-3 kinase (PI3K)/Akt kinase (Akt)/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathways. Nuclear factor of activated T-cells (NFAT) transcription factors play a key role in the regulation of gene expression in cardiac development, maintenance of an adult differentiated cardiac phenotype, and remodeling processes in cardiac hypertrophy and heart failure (HF). We tested the hypothesis that UcnII differentially regulates NFAT activity in cardiac myocytes from both normal and failing hearts through the PI3K/Akt/eNOS/NO pathway. Isoforms NFATc1 and NFATc3 revealed different basal subcellular distribution in normal and HF rabbit ventricular myocytes with a nuclear NFATc1 and a cytosolic localization of NFATc3. However, in HF, the nuclear localization of NFATc1 was less pronounced, whereas the nuclear occupancy of NFATc3 was increased. In normal myocytes, UcnII induced nuclear export of NFATc1 and attenuated NFAT-dependent transcriptional activity but did not affect the distribution of NFATc3. In HF UcnII facilitated nuclear export of both isoforms and reduced transcriptional activity. NFAT regulation was mediated by a PI3K/Akt/eNOS/NO signaling cascade that converged on the activation of several kinases, including glycogen synthase kinase-3β (GSK3β), c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated kinase (p38), and PKG, resulting in phosphorylation, deactivation, and nuclear export of NFAT. In conclusion, while NFATc1 and NFATc3 reveal distinct subcellular distribution patterns, both are regulated by the UcnII-PI3K/Akt/eNOS/NO pathway that converges on the activation of NFAT kinases and NFAT inactivation. The data reconcile cardioprotective and prohypertrophic UcnII effects mediated by different NFAT isoforms.
-
Urocortin II regulates nfat transcription factor in adult rabbit cardiac myocytes
Biophysical Journal, 2012Co-Authors: Stefanie Walther, Lothar A. BlatterAbstract:Nuclear factor of activated T cells (NFAT) transcription factors play a key role during cellular remodelling associated with hypertrophy and heart failure (HF). We tested the hypothesis that the cardioprotective peptide Urocortin II (UcnII) regulates translocation and activation of NFAT.Rabbit ventricular myocytes were infected with recombinant adenoviruses encoding for NFAT-GFP fusion proteins (isoforms NFATc1 and NFATc3). The subcellular distribution of NFAT was quantified as the ratio of NFATnuc to NFATcyt fluorescence (RNFAT) and nuclear-cytosolic NFAT translocation was expressed as changes of RNFAT. Under basal unstimulated conditions NFATc3 was predominantly localized in the cytoplasm, whereas NFATc1 displayed a nuclear localization. UcnII (100 nM) caused NFATc1 export to the cytoplasm (RNFAT decreased from 2.25 to 1.03 after 24 hrs). UcnII did not affect nuclear-cytosolic NFATc3 distribution.UcnII-induced NFATc1 export to the cytoplasm was significantly (P<0.05) reduced (by 58-79%) by inhibition of guanylate cyclase (ODQ, 10 μM), calcineurin (Cyclosporin A, 1 μM), and GSK3s (Alsterpaullone, 1 μM). Inhibition of PI3K (Wortmannin, 300 nM) and nuclear transport protein crm1 (Leptomycin B, 40 nM) prevented the redistribution of NFATc1 to the cytoplasm completely.In ventricular myocytes from failing rabbit hearts, nuclear localization of NFATc3 was significantly enhanced compared to normal myocytes (RNFAT 0.78 vs. 0.58). Stimulation of HF myocytes with UcnII resulted in a translocation of NFATc3 back to the cytoplasm (RNFAT=0.56). In HF myocytes the nuclear localization of NFATc1 was less pronounced compared to normal myocytes (RNFAT: 1.97 in HF vs. 2.86 in normal ventricular cells). UcnII induced a further redistribution of NFATc1 out of the nucleus (RNFAT=0.97).We conclude that UcnII enhances the export of NFAT from the nucleus to the cytoplasm in ventricular myocytes involving the PI3K/cGMP/PKG/calcineurin- and PI3K/Akt/GSK3s-pathways and could thus positively affect remodeling in hypertrophy and HF.
-
Urocortin II Regulates NFAT Transcription Factor in Adult Rabbit Cardiac Myocytes
Biophysical Journal, 2012Co-Authors: Stefanie Walther, Lothar A. BlatterAbstract:Nuclear factor of activated T cells (NFAT) transcription factors play a key role during cellular remodelling associated with hypertrophy and heart failure (HF). We tested the hypothesis that the cardioprotective peptide Urocortin II (UcnII) regulates translocation and activation of NFAT.Rabbit ventricular myocytes were infected with recombinant adenoviruses encoding for NFAT-GFP fusion proteins (isoforms NFATc1 and NFATc3). The subcellular distribution of NFAT was quantified as the ratio of NFATnuc to NFATcyt fluorescence (RNFAT) and nuclear-cytosolic NFAT translocation was expressed as changes of RNFAT. Under basal unstimulated conditions NFATc3 was predominantly localized in the cytoplasm, whereas NFATc1 displayed a nuclear localization. UcnII (100 nM) caused NFATc1 export to the cytoplasm (RNFAT decreased from 2.25 to 1.03 after 24 hrs). UcnII did not affect nuclear-cytosolic NFATc3 distribution.UcnII-induced NFATc1 export to the cytoplasm was significantly (P
Zsolt Bagosi - One of the best experts on this subject based on the ideXlab platform.
-
The interaction of Urocortin II and Urocortin III with amygdalar and hypothalamic cotricotropin-releasing factor (CRF) - reflections on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis
Neuropeptides, 2013Co-Authors: Zsolt Bagosi, Krisztina Csabafi, Miklos Palotai, Miklós Jászberényi, Imre Földesi, János Gardi, Gyula Szabó, Gyula TelegdyAbstract:Urocortin II (Ucn II) and Urocortin III (Ucn III) are selective agonists of the CRF receptor type 2 (CRFR2). The aim of the present experiments was to investigate the effects of Ucn II and Ucn III on the central CRF and peripheral glucocorticoids in rats. Increasing doses (0.5-1-2-5 μg/2 μl) of Ucn II or Ucn III were administered intracerebroventricularly, then CRF concentration was determined by immunoassays in two different brain regions, the amygdala and the hypothalamus, and in two different time paradigms, 5 and 30 min after the administration of peptides. In parallel with the second determination, plasma corticosterone concentration was measured by chemofluorescent assay. The amygdalar CRF amount was increased significantly by 0.5 and 5 μg of UCN II and 2 and 5 μg of UCN III in the 5 min experiments and by 5 μg of UCN II and 0.5 and 5 μg of UCN III in the 30 min experiments. The hypothalamic CRF content was not affected considerably in the 5 min paradigm, but it was influenced significantly in the 30 min paradigm, with 0.5 and 1 μg of UCN II and 0.5-2 μg of UCN III decreasing, and 2 and 5 μg of UCN II and 5 μg of UCN III increasing the hormone concentration, respectively. The plasma corticosterone concentration was decreased by 1 and 2 μg of UCN II and UCN III and increased by 0.5 and 5 μg of UCN III. The present results demonstrate that central administration of Ucn II and Ucn III modulate time-dependently and dose-dependently the amygdalar and the hypothalamic CRF concentration, and, directly or indirectly, the plasma corticosterone concentration. The present experiments suggest that the role of CRFR2 in the regulation of the HPA axis can be inhibitory or stimulatory, depending on the actual concentration of their agonists.
-
The effects of corticoptropin-releasing factor and the Urocortins on striatal dopamine release induced by electrical stimulation - An in vitro superfusion study
Neurochemical research, 2006Co-Authors: Zsolt Bagosi, Miklós Jászberényi, E. Bujdosó, Gyula TelegdyAbstract:The members of the CRF peptide family, corticotropin-releasing factor (CRF), Urocortin I (Ucn I), Urocortin II (Ucn II) and Urocortin III (Ucn III) coordinate endocrine and behavioral responses to stress. CRF has also been demonstrated to stimulate dopamine (DA) synthesis.
-
The Effects of Corticoptropin-Releasing Factor and the Urocortins on Striatal Dopamine Release Induced by Electrical Stimulation—An in vitro Superfusion Study
Neurochemical Research, 2006Co-Authors: Zsolt Bagosi, Miklós Jászberényi, E. Bujdosó, Gyula TelegdyAbstract:The members of the CRF peptide family, corticotropin-releasing factor (CRF), Urocortin I (Ucn I), Urocortin II (Ucn II) and Urocortin III (Ucn III) coordinate endocrine and behavioral responses to stress. CRF has also been demonstrated to stimulate dopamine (DA) synthesis. In our study, a superfusion system was used to investigate the effects of this peptide family on striatal DA release following electrical stimulation. The involvement of the CRF receptors was studied by pretreatment of rat striatal slices with selective CRF antagonists. CRF and Ucn I increased the release of [^3H]DA while Ucn II and Ucn III were ineffective. The CRFR1 antagonist antalarmin inhibited the [^3H]DA release induced by electrical stimulation and enhanced by CRF and Ucn I. The CRFR2 antagonist astressin-2B was ineffective. These results suggest that CRF and Ucn I mediate DA release through the activation of CRFR1. Ucn II and Ucn III are not involved in this process.
