Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, was recently identified in the rat stomach. Previous studies have shown that ghrelin potently increases growth hormone release and food intake. We examined the effects of the gastric peptide ghrelin on anxiety-like behavior in association with the hypothalamic-pituitary-adrenal axis in mice. Both intra-third cerebroventricular and intraperitoneal administration of ghrelin potently and significantly induced anxiogenic activities in the elevated plus maze test. Ghrelin gene expression in the stomach was increased by tail pinch stress as well as by starvation stress. Administration of a corticotropin-releasing hormone (CRH) receptor antagonist significantly inhibited ghrelin-induced anxiogenic effects. Peripherally administered ghrelin significantly increased CRH mRNA, but not urocortin mRNA expression in the hypothalamus. Furthermore, intraperitoneal injection of ghrelin produced a significant dose- dependent increase in serum corticosterone levels. These findings suggest that ghrelin may have a role in mediating neuroendocrine and behavioral responses to stressors and that the stomach could play an important role, not only in the regulation of appetite, but also in the regulation of anxiety.
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PMID:A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. 1152 15

Corticotropin releasing hormone (CRH) acts on the central nervous system to alter energy balance and influence both food intake and sympathetically-mediated thermogenesis. CRH is also reported to inhibit food intake in several models of hyperphagia including neuropeptide Y (NPY)-induced eating. The recently identified CRH-related peptide, urocortin (UCN), also binds with high affinity to CRH receptor subtypes and decreases food intake in food-deprived and non-deprived rats. The present experiment characterized further the feeding and metabolic effects of UCN by examining its impact after direct injections into the paraventricular nucleus (PVN) of the hypothalamus. In feeding tests (n=8), UCN (50-200 pmol) was injected into the PVN at the onset of the dark cycle and food intake was measured 1, 2 and 4 h postinjection. In separate rats (n=8), the metabolic effects of UCN were monitored using an open circuit calorimeter which measured oxygen consumption (V(O2)) and carbon dioxide production (V(CO2)). Respiratory quotient (RQ) was calculated as V(CO2)/V(O2). UCN suppressed feeding at all times studied and reliably decreased RQ within 30 min of infusion. Additional work examined the effect of UCN (50-100 pmol) pretreatment on the feeding and metabolic effects of NPY. NPY, injected at the start of the dark period, reliably increased 2 h food intake. This effect was blocked by PVN UCN administration. Similarly, UCN blocked the increase in RQ elicited by NPY alone. These results suggest that UCN-sensitive mechanisms within the PVN may modulate food intake and energy substrate utilization, possibly through an interaction with hypothalamic NPY.
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PMID:Hypothalamic paraventricular nucleus injections of urocortin alter food intake and respiratory quotient. 1159 9

Urocortin and urocortin II are members of the corticotropin-releasing hormone (CRH) family of neuropeptides that function to regulate stress responses. Two high-affinity G-protein-coupled receptors have been identified that bind CRH and/or urocortin I and II, designated CRHR1 and CRHR2, both of which are present in hippocampal regions of mammalian brain. The hippocampus plays an important role in regulating stress responses and is a brain region in which neurons are vulnerable during disease and stress conditions, including cerebral ischemia, Alzheimer's disease, and anxiety disorders. Here we report that urocortin exerts a potent protective action in cultured rat hippocampal neurons with concentrations in the range of 0.5-5.0 pm, increasing the resistance of the cells to oxidative (amyloid beta-peptide, 4-hydroxynonenal, ferrous sulfate) and excitotoxic (glutamate) insults. We observed that urocortin is 10-fold more potent than CRH in protecting hippocampal neurons from insult, whereas urocortin II is ineffective. RT-PCR and sequencing analyses revealed the presence of both CRHR1 and CRHR2 in the hippocampal cultures, with CRHR1 being expressed at much higher levels than CRHR2. Using subtype-selective CRH receptor antagonists, we provide evidence that the neuroprotective effect of exogenously added urocortin is mediated by CRHR1. Furthermore, we provide evidence that the signaling pathway that mediates the neuroprotective effect of urocortin involves cAMP-dependent protein kinase, protein kinase C, and mitogen-activated protein kinase. This is the first demonstration of a biological activity of urocortin in hippocampal neurons, suggesting a role for the peptide in adaptive responses of hippocampal neurons to potentially lethal oxidative and excitotoxic insults.
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PMID:Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I. 1178 85

The corticotropin-releasing hormone (CRH) system, including CRH and urocortin (UCN), is implicated in the central control of appetite and energy metabolism. Urocortin, a recently isolated neuropeptide closely related to CRH is involved in the central signaling cascade that inhibits energy intake. When administered intracerebroventricularly and intra-hypothalamically, UCN potently decreases food intake. Receptors for UCN, while widely distributed, are expressed in hypothalamic nuclei. As the hypothalamus is involved in modulating autonomic outflow, UCN may also act as a catabolic neuropeptide to facilitate energy expenditure through sympathetic-regulated thermogenesis. To test the hypothesis that UCN also enhances regulatory energy expenditure via the activation of the sympathetic nervous system, we examined whole body oxygen consumption (VO(2)) and colonic temperature in male Wistar rats in response to central UCN administration. That is, the intracerebroventricular injection of 1.0 microg of UCN in male Wistar rats (n=10) significantly increased whole body oxygen consumption compared to PBS control. In addition, colonic temperature was significantly increased (Delta0.7 +/- 0.08 degrees C) in UCN- vs. PBS-administered rats, which was prevented by pretreatment with the ganglionic blocker chlorisondamine. These studies suggest that UCN acutely increased whole body oxygen consumption and body temperature via central activation of sympathetic outflow.
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PMID:Central urocortin activation of sympathetic-regulated energy metabolism in Wistar rats. 1187 93

The present study was conducted to assess the effect of nutritional stress induced by food deprivation on expression of messenger ribonucleic acid (mRNA) for corticotropin-releasing hormone receptor type 2beta (CRH-R2beta) in the rat cardiovascular system in the presence or absence of changes in circulating corticosterone. Food deprivation for 96 h caused a robust increase in plasma corticosterone levels and a significant decrease in CRH-R2beta mRNA expression in the rat heart. Starvation for 48 and 96 h decreased CRH-R2beta mRNA expression in the atria, ventricle as well as aorta of sham-adrenalectomized (sham) rats. Surprisingly, clamping plasma glucocorticoids at low levels by adrenalectomy with corticosterone pellet replacement (ADX+B) did not completely prevent starvation-induced decreases of CRH-R2beta mRNA expression in the rat cardiovascular system. Urocortin (Ucn) mRNA expression was increased significantly by food deprivation in the heart of sham as well as ADX+B rats. We speculate that food deprivation may increase urocortin, which in turn down-regulates CRH-R2beta mRNA expression in cardiovascular system. These data indicate that food deprivation despite the presence or absence of changes in circulating corticosterone may have an inhibitory effect on CRH-R2beta mRNA expression in the rat cardiovascular system.
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PMID:Down-regulation of corticotropin-releasing hormone receptor type 2beta mRNA expression in the rat cardiovascular system following food deprivation. 1189 Oct 12

Corticotropin-releasing factor (CRF) is one of the principle components of the stress response. The physiological effects of CRF are mediated by two receptor subtypes, CRF(1) and CRF(2). Recent data obtained with the selective CRF(2) antagonist antisauvagine-30 (ASV-30) has begun to suggest that both CRF receptor subtypes may play a role in stress-related behaviors. Exactly how these two receptor subtypes interact to modulate the behavioral and endocrine responses to stress is not clear, however. We have attempted to understand the role of the CRF(2) receptor in the behavioral and endocrine responses to stress by comparing the effects of ASV-30 with the mixed CRF(1)/CRF(2) receptor antagonist astressin. Centrally administered ASV-30 reduced anxiety-like behavior in BALB/c mice in three models of anxiety: marble burying [minimal effective dose (MED) = 3 nmol], open field (MED = 3 nmol), and elevated plus maze (MED = 0.1 nmol). ASV-30 did not change locomotor activity or the adrenocorticotropic hormone (ACTH) response to restraint stress. The potent mixed CRF(1)/CRF(2) antagonist astressin not only reduced anxiety-like behavior in all three models with equivalent potency but also blunted the ACTH response to restraint stress. Finally, the new selective CRF(2) receptor agonist urocortin-II produced a dose-dependent increase in anxiety-like behavior in the plus maze test. Therefore, our data suggest that the CRF(2) receptor plays a role in the behavioral, but not the hypothalamic-pituitary-adrenal axis, response to stress.
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PMID:Pharmacological evidence supporting a role for central corticotropin-releasing factor(2) receptors in behavioral, but not endocrine, response to environmental stress. 1206 11

The two newest members of the urocortin (UCN)/corticotropin-releasing hormone (CRH) family of peptides - UCN II and UCN III - bind to the CRH-2 receptor, suppress feeding, and are expressed in the periphery as well as the brain. We used several sensitive techniques to examine their interactions with the blood-brain barrier (BBB). Of the four known peptides in this family, each interacts with the BBB differently. UCN I barely enters the brain from blood unless its latent saturable influx system is activated by leptin or pretreatment with glucose. However, neither leptin nor glucose affected the entry of intact UCN II. UCN II reached brain paranchyma at a moderate rate that was not self-inhibited or cross-inhibited by UCN/CRH peptides. The apparent, but misleading, rapid influx of UCN III (stresscopin) could be explained by degradation at the BBB itself. Influx of CRH into brain was slower than UCN II but faster than UCN I; it was inhibited by excess CRH but not by excess UCN I, II, III, or leptin. CRH is the only member of this family to have a saturable efflux system out of the brain. Determination of hydrogen bonding, newly applied here to ingestive peptides, was not helpful in explaining these differential interactions of the UCN peptides with the BBB.
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PMID:Differential interactions of urocortin/corticotropin-releasing hormone peptides with the blood-brain barrier. 1206 89

Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing.
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PMID:Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior. 1209 10

The intermediate portion of the lateral septum (LSi) contains high levels of urocortin (UCN) peptide and type 2 corticotropin-releasing hormone (CRH) receptor (CRHR2) and has anatomic and functional connections with the lateral hypothalamus (LH). We tested the effect of UCN in the LSi on feeding. Injection of 10 or 30 pmol UCN into LSi significantly decreased feeding in food-deprived rats for 24 h without producing conditioned taste aversion (CTA). Pretreatment with a CRH receptor antagonist, alpha-helical CRH (alpha-hCRH), blocked the inhibitory effect of UCN on deprivation-induced feeding at 1 and 2 h postinjection. Furthermore, UCN in the LSi significantly decreased feeding induced by LH-injected orexin A at 2 and 4 h postinjection, and addition of alpha-hCRH blocked the inhibitory effect of UCN on orexin A-induced feeding. In conclusion, UCN significantly inhibits feeding induced by deprivation and LH-injected orexin A without producing a CTA, an effect that is mediated by CRHR2. These data define the LSi as an important site for UCN-induced anorexia and indicate that LSi UCN may influence orexin A feeding signals in the LH.
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PMID:Urocortin in the lateral septal area modulates feeding induced by orexin A in the lateral hypothalamus. 1212 48

Urocortin (Ucn) is a member of the corticotropin-releasing hormone (CRH)-related peptides that has been reported to have cardiac inotropic and hypertrophic effects. In addition, Ucn mRNA was expressed in cardiac myocytes (MCs) and Ucn was suggested to have cardioprotective effects. Recently, it was reported that Ucn mRNA was expressed in cardiac non-myocytes (NMCs). Based on these facts, Ucn is assumed to affect not only MCs but also NMCs in an autocrine fashion. The present study was designed to elucidate a pathophysiological role of Ucn on NMCs. NMCs were prepared by the discontinuous Percoll gradient and adhesion method. Ucn increased [(3)H]-thymidine uptake into NMCs. Ucn also enhanced endothelin-1-induced increase of [(3)H]-thymidine uptake into NMCs. Effects of Ucn on [(3)H]-thymidine uptake into NMCs were significantly abolished by the protein kinase A inhibitor, H89 (10(-5) M), but not by a competitive antagonist of CRH receptors, astressin (10(-5) M). Ucn also increased intracellular cAMP accumulation more potently than CRH on a molar basis. Finally, both MCs and NMCs also secreted Ucn. Together with the recent findings, at least in NMCs, these data suggest that Ucn could exert its own actions via the cAMP signaling pathway, but not through known CRH type 2 receptors, in an autocrine fashion. In conclusion, the present study indicated that Ucn was secreted not only from MCs but also from NMCs and that the primary source of Ucn acting on heart was the heart itself. On the other hand, Ucn could proliferate NMCs as well as MCs, suggesting that Ucn could be involved in cardiac hypertrophy and fibrosis, i.e., cardiac remodeling, in spite of its putative cardioprotective actions.
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PMID:Urocortin has cell-proliferative effects on cardiac non-myocytes. 1217 7


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