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)

We have previously proposed the existence of ultrashort loop-positive feedback regulation of corticotropin-releasing hormone (CRH) in the hypothalamus. To gain a better understanding of this effect, we performed double-label in situ hybridization to identify the neurons in the paraventricular nucleus (PVN) that express CRH type 1 receptor (CRH-R1) following stress. We also conducted immunohistochemistry to determine whether CRH-R1 mRNA was translated to CRH-R1 protein in the PVN. Thirty-minute restraint stress given to male Wistar rats increased c-fos mRNA expression primarily in the CRH-producing neurons of the parvocellular PVN. Small numbers of vasopressin and oxytoxin-producing cells were also labeled by c-fos probes. Approximately 70% of CRH-R1 positive neurons exhibited CRH mRNA 2 h after the beginning of stress, while only a small percentage of the vasopressin and oxytocin-producing cells coexpressed CRH-R1 mRNA. CRH-R1 immunoreactivity, which was detected in the perikarya and fibers of PVN neurons, appeared to increase in response to stress, though this was not statistically significant. Pretreatment with a selective CRH-R1 antagonist, CP-154,526, significantly attenuated stress-induced corticotropin (ACTH) secretion as well as c-fos mRNA expression in the PVN. These results demonstrate that acute stress increases neuronal activation and CRH-R1 mRNA expression primarily in CRH-producing neurons of the parvocellular PVN, that CRH-R1 message is translated to CRH-R1 protein, and that PVN neurons are activated at least in part through CRH-R1 under acute stress. The data further support the possibility of feedback regulation of CRH itself in CRH-producing neurons.
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PMID:Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress. 1139 2

The effects of chronic immune challenge on cytokine expression and hypothalamic-pituitary-adrenal axis (HPA) axis responses to stress were studied in Wistar rats after administration of increasing doses of lipopolysaccharide (LPS). Repeated LPS (R-LPS) decreased body weight and increased adrenal weight and pituitary pro-opiomelanocortin mRNA levels. LPS injection increased plasma adrenocorticotropic hormone (ACTH) and corticosterone but the effect was attenuated in R-LPS. Plasma corticosterone but not ACTH responses to restraint were also reduced in R-LPS. Basal and restraint-stimulated corticotropin releasing hormone (CRH) mRNA levels were lower in R-LPS, but responses to a new LPS injection were similar to controls. In contrast, type 1 CRH receptor (CRH-R1) mRNA responses to both LPS and restraint were blunted in R-LPS. Vasopressin mRNA levels in parvocellular neurones were higher in R-LPS, and increased further after restraint but not after a new LPS injection. Glucocorticoid receptor (GR) levels in the paraventricular nucleus (PVN) increased after a single LPS or R-LPS (24 h after the last injection) but declined after a new injection in R-LPS. Interleukin (IL)-1beta and IL-6 mRNAs increased in the pituitary, spleen and circumventricular organs after single or R-LPS, suggesting that cytokines may contribute to the activation of the HPA axis though pathways from the circumventricular organs as well as paracrine effects in the pituitary. The data show that (i) adaptation of the HPA axis during repeated LPS injection involves increases in vasopressin : CRH expression ratios in parvocellular neurones; (ii) that hypothalamic CRH and vasopressin responses to acute stimulation are independent of CRH-R1 expression in the PVN; and (iii) there is a dissociation between pituitary and adrenal responses to acute stress suggesting a decrease of adrenal sensitivity to ACTH.
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PMID:Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats. 1148 88

Corticotropin-releasing hormone plays a critical role in mediating the stress response. Brain circuits hypothesized to mediate stress include the thalamus, which plays a pivotal role in distributing sensory information to cortical and subcortical structures. In situ hybridization revealed neurons containing corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group and the central medial nucleus of the thalamus, which interfaces with the ventral posteromedial nucleus (parvicellular part). These regions are of interest because they process somatosensory and visceral information. In the first experiment, the effect of acute stress on thalamic corticotropin-releasing hormone messenger RNA levels was assessed. Rats restrained for 1 h and killed 1 h later were found to have increased corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group. The time course of these changes was examined in a second experiment in which rats were killed immediately or 3 h after restraint. While no changes occurred in the thalamus immediately after restraint, 3 h after restraint, increases in corticotropin-releasing hormone messenger RNA occurred in both the posterior thalamic nuclear group and the central medial-ventral posteromedial nucleus (parvicellular part) of the thalamus. A different pattern of activation was observed in the paraventricular nucleus of the hypothalamus with increased corticotropin-releasing hormone messenger RNA immediately after restraint, but not 1 or 3 h later. In addition to the stress-induced changes, a prominent decrease in baseline thalamic corticotropin-releasing hormone messenger RNA was observed from 1000 to 1300 h. These results show that the thalamus contains corticotropin-releasing hormone messenger RNA that increases after restraint stress, indicating a role for thalamic corticotropin-releasing hormone systems in the stress response. Stress-induced changes in thalamic corticotropin-releasing hormone messenger RNA expression appears to be regulated differently than that in the paraventricular nucleus of the hypothalamus, and may be influenced by diurnal mechanisms.
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PMID:Corticotropin-releasing hormone messenger RNA distribution and stress-induced activation in the thalamus. 1153 Feb 29

The differential effects of osmotic stimulation on magnocellular and parvocellular hypothalamic neurons were studied by analysis of corticotropin-releasing hormone (CRH) and vasopressin (VP) expression in controls and 48-h water-deprived rats subjected to either restraint for 1 h or a single lipopolysaccharide injection (250 microg/100 g). Water deprivation reduced basal CRH mRNA levels but the increments following 4 h of restraint or 6 h lipopolysaccharide (LPS) injection were similar to those in controls. In contrast, water deprivation had no effect on basal VP heteronuclear RNA (hnRNA) and mRNA levels in parvocellular neurons, but responses to restraint or LPS injection were reduced. VP expression in magnocellular paraventricular and supraoptic nuclei, and plasma sodium and vasopressin were higher in water-deprived rats, changes which were unaffected by restraint. LPS injection reduced VP mRNA but not hnRNA levels in magnocellular neurons and increased plasma vasopressin levels only in water-deprived rats independently of changes in plasma sodium. This was accompanied by an increase in vasopressin mRNA content in the posterior pituitary. The data show that the blunted ACTH responses to acute stress during chronic osmotic stimulation are correlated with the inability of parvocellular neurons to increase VP rather than CRH expression. In addition, LPS-induced endotoxemia causes disturbances of the magnocellular vasopressinergic system with an unexpected potentiation of osmotic simulated VP secretion. The lack of increase in VP transcription after LPS and changes in VP mRNA distribution suggest that endotoxemia affect the secretory process at the levels of the neurohypophyseal axon terminal.
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PMID:Hypothalamic pituitary adrenal axis and hypothalamic-neurohypophyseal responsiveness in water-deprived rats. 1157 86

Consistent findings in depressed patients are hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis with high plasma concentrations of adrenocorticotropic hormone and cortisol. Long-term antidepressant treatments seem to normalize this hyperactivity, suggesting a link between the HPA axis and the action of antidepressant treatments. The present study was carried out to study the effects of antidepressant treatments on pro-opiomelanocortin (POMC) mRNA expression, with a focus on interaction with acute stress and 5-HT(1A) receptor activation. Male rats were treated for 21 days with saline, citalopram, fluoxetine, moclobemide or desipramine, and the expression of POMC mRNA in the anterior pituitary was analysed by semi-quantitative in situ hybridization. All antidepressants, but not saline, cocaine and haloperidol, reduced POMC mRNA expression. The decrease in POMC mRNA was not observed until 9 days of citalopram treatment. Decreased POMC mRNA levels were also observed after 14 days of repeated electroconvulsive stimulation. The decreased POMC mRNA levels did not affect the stress-induced POMC mRNA increase, measured following swim stress and restraint stress. Finally, using Fos as a marker for neural activity, we showed attenuation of 8-OH-DPAT-stimulated activity in the paraventricular nucleus following 21 days of citalopram treatment. In conclusion, antidepressant treatments decrease basal POMC mRNA expression without affecting the acute stress response, and the reduced POMC mRNA may be related to reduced 5-HT(1A)-stimulated hypothalamic output.
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PMID:Chronic antidepressant treatments decrease pro-opiomelanocortin mRNA expression in the pituitary gland: effects of acute stress and 5-HT(1A) receptor activation. 1167 57

Stress may be a contributing factor in intestinal inflammatory disease; however, the underlying mechanisms have not been elucidated. We previously reported that acute stress altered jejunal epithelial physiology. In this study, we examined both physical and psychological stress-induced functional changes in colonic mucosa. Colonic mucosal tissue from rats subjected to either 2 hr of cold-restraint stress or 1 hr of water-avoidance stress demonstrated altered ionic transport as well as significantly elevated baseline conductance (ionic permeability) and flux of horseradish peroxidase (macromolecular permeability). Intraperitoneal pretreatment with the corticotropin-releasing hormone (CRH) antagonist, a helical CRH(9-41), inhibited the stress-induced abnormalities, while exogenous intraperitoneal administration of CRH, to control rats, mimicked the stress responses and in vitro CRH increased the macromolecular permeability. These results suggest that peripheral CRH mediates stress-induced colonic pathophysiology. We speculate that a stress-induced barrier defect may allow uptake of immunogenic substances into the colonic mucosa, initiating or exacerbating intestinal inflammation.
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PMID:Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH. 1185 79

In a series of experiments, we tested the hypothesis that chronic antidepressant drug administration reduces the synaptic availability of corticotropin-releasing factor (CRF) through one or more effects on CRF gene expression or peptide synthesis. We also determined whether effects of acute or chronic stress on CRF gene expression or peptide concentration are influenced by antidepressant drug treatment. Four-week treatment with venlafaxine, a dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor, and tranylcypromine, a monoamine oxidase inhibitor, resulted in an attenuation of acute stress-induced increases in CRF heteronuclear RNA (hnRNA) synthesis in the paraventricular nucleus (PVN). Trends toward the same effect were observed after treatment with the 5-HT reuptake inhibitor fluoxetine, or the NE reuptake inhibitor reboxetine. CRF mRNA accumulation in the PVN during exposure to chronic variable stress was attenuated by concurrent antidepressant administration. Basal CRF hnRNA and mRNA expression were not affected by antidepressant treatment in the PVN or in other brain regions examined. Chronic stress reduced CRF concentrations in the median eminence, but there were no consistent effects of antidepressant drug treatment on CRF, serum corticotropin, or corticosterone concentrations. CRF receptor expression and basal and stress-stimulated HPA axis activity were unchanged after antidepressant administration. These results suggest that chronic antidepressant administration diminishes the sensitivity of CRF neurons to stress rather than alters their basal activity. Additional studies are required to elucidate the functional consequences and mechanisms of this interaction.
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PMID:Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment. 1186 19

At least two hypothalamic peptides, corticotropin releasing hormone (CRH) and vasopressin (VP), are important in regulating adrenocorticotropin (ACTH) release from the anterior pituitary. Both are secreted in a pulsatile manner and stimulate ACTH secretion by interacting with G protein-coupled receptors (GPCRs), namely the type 1 CRH receptor and V1b receptor, respectively. Repeated or prolonged stimulation with either peptide can cause reduced ACTH responsiveness or desensitisation, both in vivo and in vitro. Desensitisation of perifused sheep anterior pituitary cells to VP was found to be rapid and occurred following treatment with 5 nM VP for 5 min. This is within the range of concentrations and durations of VP pulses seen in sheep portal blood during acute stress. In contrast, significant desensitisation of the ACTH response to CRH required pre-treatment for longer than 25 min with a CRH concentration of 1 nM, suggesting that endogenous pulses may not elicit desensitisation. Although rapid GPCR desensitisation involves uncoupling of receptors from their G proteins, commonly mediated by receptor phosphorylation, and internalisation of receptors, desensitisation of neither the CRH nor VP receptor was mediated by PKA or PKC, respectively. Desensitisation of the response to VP was found to be dependent upon receptor internalisation, and resensitisation could be delayed by treatment with a protein phosphatase 2B inhibitor. The rapid kinetics of desensitisation of the ACTH response to VP suggest that this process is important in regulating the response to acute rather than chronic stress. If, as has been suggested, CRH acts in a permissive way to set corticotrope gain, desensitisation to CRH could also be important in long term regulation of ACTH secretion.
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PMID:Acute and chronic regulation of pituitary receptors for vasopressin and corticotropin releasing hormone. 1193 3

We examined the role of the posterior division of the paraventricular nucleus of the thalamus (pPVTh) in habituation of hypothalamic-pituitary-adrenal (HPA) responses to repeated restraint. Habituation refers to the decrement in HPA activity that occurs with repeated exposure to the same or homotypic stressor. To date, the pPVTh has been shown to inhibit the enhanced or facilitated HPA responses to novel, heterotypic restraint in previously chronically cold stressed rats. We hypothesized that the pPVTh also inhibits HPA activity under conditions of habituation. In the first experiment, we lesioned the pPVTh and examined adrenocorticotropic hormone (ACTH) and corticosterone responses to the first or eighth restraint exposure. In sham-lesioned rats, we found lower ACTH and corticosterone responses to the eighth period of 30 min restraint compared to the first exposure, evidence for habituation. In pPVTh-lesioned rats, there was no difference in ACTH and corticosterone responses to the eighth compared to the first restraint exposure. Therefore, pPVTh lesions prevented the habituation of HPA responses to repeated restraint. In the second experiment, we examined whether habituation to restraint is observable in response to an acute, single restraint on day 28 in sham and pPVTh lesioned rats that were exposed to restraint only on days 1 through 8. In this experiment, we replicated the results from the first experiment, and found evidence that habituation to restraint can be observed weeks after chronic stress has been terminated. Furthermore, pPVTh lesions had no additional effects on HPA responses to acute stress on day 28. In summary, pPVTh lesions inhibit habituation of HPA activity to a homotypic stressor, without altering HPA responses to the first restraint. Thus, the intact pPVTh inhibits HPA activity under conditions of habituation, as well as facilitation, and represents an important regulator of HPA activity under conditions of chronic stress.
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PMID:Lesions of the posterior paraventricular thalamus block habituation of hypothalamic-pituitary-adrenal responses to repeated restraint. 1200 May 46

1. Of the melanocortin peptides, gamma(2)-melanocyte-stimulating hormone (MSH) has been attributed a cardiovascular effect, inducing an increase in blood pressure and heart rate. Although still controversial, this effect, based on pharmacological blockade experiments, is supposed to be mediated through sympathetic activation. 2. The aims of the present study were to identify the N-terminal pro-opiomelanocortin (N-POMC) fragments and melanocortins that influence blood pressure and heart rate and to investigate the real-time changes in baroreflex sensitivity and in sympathetic and vagal modulation underlying cardiovascular effects in conscious rats without the use of pharmacological blockade. 3. Intracerebroventricular administration of different melanocortins and N-POMC induced a long-lasting dose- dependent pressor response from 1 nmol onwards, with only a small initial bradycardic response with the highest dose. 4. Coinciding with this pressor response, an elicitation of the low-frequency (LF) component was observed in spectral analysis of both blood pressure variability (BPV) and heart rate variability (HRV), followed by the high-frequency (HF) component in at least BPV. Baroreflex sensitivity remained unchanged. 5. After intravenous administration, gamma(2)-MSH produced a short-lasting dose-dependent pressor and cardioaccelerator response with very rapid onset with concentrations from 1 nmol onwards. 6. Continuous infusion of gamma(2)-MSH depressed baroreflex sensitivity and simultaneously increased both components of BPV, with a radical reduction of the LF component and a preserved vagal HF component in HRV. 7. Of all the intravenously administered melanocortins, only gamma(2)-MSH was active. The central effect is likely to depend on an increase of (alpha-)sympathetic outflow. 8. For the peripheral effect, gamma(2)-MSH appeared to act as a baroreceptor reflex-blocking agent, being compatible with a role in the acute stress response.
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PMID:Effects of melanocortins on cardiovascular regulation in rats. 1268 Aug 51


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