UNIPROT:P01189 - FACTA Search

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

Patterns of co-localization of immunoreactivity for dopamine beta-hydroxylase (the synthetic enzyme for noradrenaline) and glutamic acid decarboxylase (the synthetic enzyme for GABA) or each one of six neuropeptides (neuropeptide Y, substance P, met-enkephalin, galanin, dynorphin A and somatostatin) were investigated with dual-colour confocal laser scanning microscopy in axons of cervical, thoracic and lumbar spinal segments of six adult rats. Four regions of the grey matter were studied (laminae I-II, V, IX and X) and, in thoracic segments, the intermediolateral cell column was also examined. The extent of co-localization was estimated by direct assessment of merged pairs of optical sections and by automated image analysis. Significant co-localization was found for neuropeptide Y in axons of the intermediolateral cell column of thoracic segments and in lamina X of cervical and thoracic segments. None of the other peptides or glutamic acid decarboxylase were found to coexist at significant levels with dopamine beta-hydroxylase and hence it is likely that this group of neuropeptides and GABA are not co-transmitters of bulbospinal noradrenergic axons in the rat.
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PMID:Absence of co-localized glutamic acid decarboxylase and neuropeptides in noradrenergic axons of the rat spinal cord. 907 Jun 45

The lateral division of the central nucleus of the amygdala (CEAl) and the oval nucleus of the bed nucleus of the stria terminalis (BSTov) have been linked closely anatomically and functionally. To determine whether these regions may be subdivided further on a neurochemical basis, dual in situ hybridization was used to determine the colocalization of corticotropin-releasing hormone (CRH), enkephalin (ENK), or neurotensin (NT) with glutamic acid decarboxylase isoforms 65 and 67 [used concurrently as a marker for gamma-aminobutyric acid GABA] in these nuclei. It was found that, for both regions, each peptide invariably was localized in a GABAergic cell. Although there was a similar overlap in the distribution of NT with ENK in the BSTov and CEAl, it was observed that CRH and ENK rarely were colocalized in either nucleus. To determine whether these distinct neuronal populations could be activated differentially, male rats were given a systemic injection of interleukin-1beta (IL-1beta; 5 microg/kg, i.p.), a stimulus that results in a robust increase in c-fos mRNA expression in the BSTov and CEAl. The neurochemical identity of these activated neurons showed striking similarities between the BSTov and the CEAl; All IL-1beta-responsive cells were GABAergic, the majority of c-fos- positive cells expressed ENK mRNA (BSTov, 81%; CEAl, 94%), and some expressed NT mRNA (BSTov, 23%; CEAl, 22%), whereas very few expressed CRH mRNA (BSTov, 4%; CEAl, 1%). These data provide evidence for the existence of discrete neural circuits within the BSTov and CEAl, and the similarities in the patterns of neurochemical colocalization in these nuclei are consistent with the concept of an extended amygdala. Furthermore, these data indicate that intraperitoneal IL-1beta recruits neurochemically distinct pathways within the BSTov and CEAl, and it is suggested that this differential activation may mediate specific aspects of immune, limbic, and/or autonomic processes.
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PMID:Distinct neurochemical populations in the rat central nucleus of the amygdala and bed nucleus of the stria terminalis: evidence for their selective activation by interleukin-1beta. 1046 74

The testicular regulation of luteinizing hormone (LH) secretion in the adult rhesus monkey is mediated by an indirect action of testosterone to decelerate pulsatile gonadotrophin releasing hormone (GnRH) release. Whether this negative feedback action of testosterone involves regulation of GnRH gene expression is unknown. Therefore, the effect of bilateral orchidectomy on hypothalamic levels of the mRNA encoding this hypophysiotropic factor was examined. The feedback action of testosterone is generally considered to be mediated through non-GnRH cells, and the present experiment provided the opportunity to also examine testicular influences on mRNAs encoding putative hypothalamic factors implicated in the testicular regulation of LH secretion. Adult male rhesus monkeys were orchidectomized (n=5) or sham-orchidectomized (n=5) and killed 6 weeks later, after a castration-induced hypersecretion of LH was established. Separate preoptic and mediobasal hypothalamus containing areas were collected, and levels of GnRH mRNA, as well as those of mRNAs encoding pro-opiomelanocortin (POMC), the gamma-aminobutyric acid (GABA) synthesizing enzymes (glutamic acid decarboxylase 65 and 67; GAD65 and GAD67, respectively), neuropeptide Y, galanin and transforming growth factor (TGF)alpha, were quantified using RNase protection assay. Values were expressed in terms of optical density relative to that of cyclophilin mRNA levels. Bilateral orchidectomy produced a significant increase in GnRH mRNA levels that was restricted to the mediobasal hypothalamus and that was associated with a significant decrease in POMC, GAD65 and GAD67 mRNA levels in this region of the hypothalamus. In contrast, neuropeptide Y, galanin and TGFalpha mRNA levels were not affected by castration. These results indicate that, in the monkey, the deceleration of pulsatile GnRH release that is imposed by the testis, and presumably mediated by testosterone, is associated with a concomitant down regulation of GnRH gene expression in the mediobasal hypothalamus. They also support the notion that this hypothalamic feedback action may be mediated by POMC-and GABA-producing neurones in the mediobasal hypothalamus.
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PMID:Effects of orchidectomy on levels of the mRNAs encoding gonadotropin-releasing hormone and other hypothalamic peptides in the adult male rhesus monkey (Macaca mulatta). 1071 12

In aging brain, degeneration or functional impairment of the hippocampus has been connected with stress dysregulation, serving to disinhibit stress responses and allow for glucocorticoid hypersecretion and its attendant pathophysiology. Hippocampal dysfunction appears to be communicated to paraventricular hypothalamic corticotropin-releasing hormone neurons by way of subcortical GABAergic neurons. As such, hippocampal-hypothalamic relays are likely to play an important role in age-related stress dysfunction. To test this hypothesis, regulation of glutamic acid decarboxylase isoform mRNA was studied in young (3 months), middle aged (15 months) and aged (30 months) Fischer 344/Brown Norway F1 hybrid rats. Basal expression of glutamic acid decarboxylase (GAD) 65 mRNA was increased in the medial preoptic area and posteromedial bed nucleus of the stria terminalis (BST) in aged rats relative to both middle-aged and young groups. Unlike young or middle-aged animals, exposure to chronic intermittent stress decreased GAD65 mRNA levels in the medial preoptic area and posteromedial BST of aged rats. Thus, while aged rats show evidence of elevated basal GABA synthesis, chronic stress causes differential loss of GAD in hippocampal-PVN relays, consistent with reduced PVN inhibition.
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PMID:Differential regulation of forebrain glutamic acid decarboxylase mRNA expression by aging and stress. 1152 Apr 93

Clinical studies demonstrate that the antidepressant efficacy of St John's wort (Hypericum) is comparable to that of tricyclic antidepressants such as imipramine. Onset of efficacy of these drugs occurs after several weeks of treatment. Therefore, we used in situhybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract, and hypericin (an active constituent of St John's wort) on the expression of genes that may be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine (15 mg kg(-1)), Hypericum (500 mg kg(-1)), and hypericin (0.2 mg kg(-1)) given daily by gavage for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 16-22% in the hypothalamic paraventricular nucleus (PVN) and serotonin 5-HT(1A) receptor mRNA by 11-17% in the hippocampus. Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three compounds on gene transcription suggests a shared action on the centers that control HPA axis activity. A second study was performed to assess the effects of long-term imipramine and Hypericum administration on stress-induced changes in gene transcription in stress-responsive circuits. Repeated immobilization stress (2 h daily for 7 days) increased mRNA levels of CRH in the PVN, proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus. It decreased mRNA levels of 5-HT(1A) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Long-term pre-treatment with either imipramine or Hypericum reduced to control levels the stress-induced increases in gene transcription of GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum. The stress-induced decreases in BDNF and 5-HT(1A)mRNA levels were not prevented by either drug. Taken together, these data show: (1) that Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine; and (2) that select stress-induced changes in gene transcription in particular brain areas can be prevented by long-term treatment with either the prototypic tricyclic antidepressant imipramine or the herbiceutical St John's wort. However, imipramine appears to be more effective in blocking stress effects on the HPA axis than the plant extract.
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PMID:St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats. 1152 69

Using a preembedding double immunoreactive technique by immunostaining with antirat beta-endorphin and antisynthetic glutamic acid decarboxylase antisera sequentially, the synaptic relationships between beta-endorphinergic neuronal fibers and GABAergic neurons in the dorsal raphe nucleus of the rat were examined at the ultrastructural level. Although both beta-endorphin-like immunoreactive fibers and glutamic acid decarboxylase-like immunoreactive neurons can be found in the mediodorsal and medioventral parts of the dorsal raphe nucleus, the synapses between them were found only in the mediodorsal part. Most of the beta-endorphin-like immunoreactive neuronal fibers contained many dense-cored vesicles. The synapses made by beta-endorphin-like immunoreactive neuronal axon terminals on glutamic acid decarboxylase-like immunoreactive neurons were both symmetrical and asymmetrical, with the latter predominant, especially in the axo-dendritic synapses. Perikarya with beta-endorphin-like immunoreactivity were found only in the ventrobasal hypothalamus. These findings suggest the possibility that the beta-endorphin-producing neurons in the ventrobasal hypothalamus could influence GABAergic neurons in the dorsal raphe nucleus directly by synaptic relationships.
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PMID:Immunoelectron microscopic study of beta-endorphinergic synaptic innervation of GABAergic neurons in the dorsal raphe nucleus. 1174 21

Gamma-aminobutyric acid (GABA) interacts with hypothalamic neuronal pathways regulating feeding behaviour. GABA has been reported to stimulate feeding via both ionotropic GABA(A) and metabotropic GABA(B) receptors. The functional form of the GABA(B) receptor is a heterodimer consisting of GABA(B) receptor-1 (GABA(B)R1) and GABA(B) receptor-2 (GABA(B)R2) proteins. Within the heterodimer, the GABA-binding site is localized to GABA(B)R1. In the present study, we used an antiserum to the GABA(B)R1 protein in order to investigate the cellular localization of GABA(B)R1-immunoreactive neurones in discrete hypothalamic regions implicated in the control of body weight. The colocalization of GABA(B)R1 immunoreactivity with different chemical messengers that regulate food intake was analysed. GABA(B)R1-immunoreactive cell bodies were found in the periventricular, paraventricular (PVN), supraoptic, arcuate, ventromedial hypothalamic, dorsomedial hypothalamic, tuberomammillary nuclei and lateral hypothalamic area (LHA). Direct double-labelling showed that glutamic acid decarboxylase (GAD)-positive terminals were in close contact with GABA(B)R1-containing cell bodies located in all these regions. In the ventromedial part of the arcuate nucleus, GABA(B)R1-immunoreactive cell bodies were found to contain neuropeptide Y, agouti-related peptide (AGRP) and GAD. In the ventrolateral part of the arcuate nucleus, GABA(B)R1-immunoreactive cell bodies were shown to contain pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. In the LHA, GABA(B)R1 immunoreactivity was present in both melanin-concentrating hormone- and orexin-containing cell populations. In the tuberomammillary nucleus, GABA(B)R1-immunoreactive cell bodies expressed histidine decarboxylase, a marker for histamine-containing neurones. In addition, GAD and AGRP were found to be colocalized in some nerve terminals surrounding GABA(B)R1-immunoreactive cell bodies in the parvocellular part of the PVN. The results may provide a morphological basis for the understanding of how GABA regulates the hypothalamic control of food intake and body weight via GABA(B) receptors.
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PMID:Chemical coding of GABA(B) receptor-immunoreactive neurones in hypothalamic regions regulating body weight. 1253 64

Autoimmune thyroid diseases (ATD) are often associated with Type 1 diabetes mellitus (T1DM) and Addison's disease (AD), characterizing the autoimmune polyendocrine syndrome. We evaluated the frequency of autoantibodies against glutamic acid decarboxylase isoform 65 (GAD65Ab) and 21-hydroxylase (21OHAb) in the sera of 65 [58 females (F)/7 males (M), 17-70 yr] patients with Graves' disease (GD) and 47 (45 F/2 M, 12-77 yr) with Hashimoto's thyroiditis (HT), none of whom had either diabetes or AD. The sera of 30 recently diagnosed T1DM patients (16 M/14 F, 1-39 yr) and of 97 (54 F/43 M, 7-69 yr) healthy controls were also examined. GAD65Ab were detected in the sera of 18 (60%) T1DM, 8 (12%) GD and in none of the HT patients or the controls (p = 0.03 for GD vs HT, p = 0.002 for GD vs controls, and p < 0.001 for GD vs T1DM). 21OHAb were detected in the sera of 2 (3%) GD, 1 (2%) HT and in none of the T1DM patients or the controls. GAD65Ab levels were significantly lower in GD than in T1DM patients (median: -0.06 vs 0.28, p < 0.001). Six of the 8 GD GAD65Ab-positive patients submitted to an intravenous glucose tolerance test showed no diminished first phase insulin secretion. All 21OHAb positive patients had normal basal cortisol and adrenocorticotropin (ACTH), normal cortisol response after ACTH stimulation, but high plasma renin activity. In conclusion, despite the genetic diversity of the Brazilian population, the frequency of GAD65Ab and 21OHAb in our patients is similar to that observed in other countries. GAD65Ab were more prevalent in GD than in HT patients, suggesting a difference in the immune response between these disorders. Long-term follow-up is necessary to determine the clinical relevance of these autoantibodies in the Brazilian population.
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PMID:Autoantibodies against glutamic acid decarboxylase and 21-hydroxylase in Brazilian patients with type 1 diabetes or autoimmune thyroid diseases. 1463 33

Neural networks controlling food intake and energy homeostasis clearly involve proopiomelanocortin (POMC) neurons and their peptide transmitters. alpha-melanocyte-stimulating hormone from arcuate POMC neurons potently reduces food intake, whereas arcuate neuropeptide Y (NPY) neurons act in opposition to stimulate food intake. In addition to orexigenic peptides, NPY neurons also release the inhibitory neurotransmitter GABA, which can act in a local circuit to inhibit POMC neuron activity. Whether or not reciprocal inhibition could occur has not yet been determined, because the presence of a rapid neurotransmitter in POMC neurons has not been demonstrated previously. Here, we used primary cultures of fluorescently labeled POMC neurons that had formed recurrent synapses (autapses) to detect the release of neurotransmitter. When an action potential was evoked in the axon of a POMC neuron with autapses, a short-latency synaptic current was recorded in the same cell. The autaptic current was abolished by GABA(A) receptor antagonists and substantially inhibited by opioids. Double-label in situ RNA hybridization for POMC and glutamic acid decarboxylase, the GABA synthetic enzyme, revealed colocalization of mRNAs in approximately one-third of POMC neurons in vivo. Our results suggest that these neurons can exert rapid inhibitory effects via the release of GABA, in addition to the more sustained actions provided by POMC peptides. However, this rapid inhibition may not play a major role within local hypothalamic circuits, but rather is likely to be important in more distant projection areas as indicated by the colocalization of vesicular GABA transporter immunoreactivity predominantly in extrahypothalamic POMC terminals.
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PMID:GABA release from proopiomelanocortin neurons. 1497 27

Whole-cell recordings were made from identified gastric-projecting rat dorsal motor nucleus of the vagus (DMV) neurons. The amplitude of evoked IPSCs (eIPSCs) was unaffected by perfusion with met-enkephalin (ME) or by mu-, delta-, or kappa-opioid receptor selective agonists, namely D-Ala2-N-Me-Phe4-Glycol5-enkephalin (DAMGO), cyclic [D-Pen2-D-Pen5]-enkephalin, or trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolytinil)-cyclohexyl]-benzeneacetamide methane sulfonate (U50,488), respectively. Brief incubation with the adenylate cyclase activator forskolin or the nonhydrolysable cAMP analog 8-bromo-cAMP, thyrotropin releasing hormone, or cholecystokinin revealed the ability of ME and DAMGO to inhibit IPSC amplitude; this inhibition was prevented by pretreatment with the mu-opioid receptor (MOR1) selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. Conversely, incubation with the adenylate cyclase inhibitor dideoxyadenosine, with the protein kinase A (PKA) inhibitor N-[2-(p-Bromocinnamyl-amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89), or with the Golgi-disturbing agent brefeldin A, blocked the ability of forskolin to facilitate the inhibitory actions of ME. Immunocytochemical experiments revealed that under control conditions, MOR1 immunoreactivity (MOR1-IR) was colocalized with glutamic acid decarboxylase (GAD)-IR in profiles apposing DMV neurons only after stimulation of the cAMP-PKA pathway. Pretreatment with H89 or brefeldin A or incubation at 4 degrees C prevented the forskolin-mediated insertion of MOR1 on GAD-IR-positive profiles. These results suggest that the cAMP-PKA pathway regulates trafficking of mu-opioid receptors into the cell surface of GABAergic nerve terminals. By consequence, the inhibitory actions of opioid peptides in the dorsal vagal complex may depend on the state of activation of brainstem vagal circuits.
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PMID:Mu-opioid receptor trafficking on inhibitory synapses in the rat brainstem. 1531 60

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