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)

The secretion of alpha-MSH from the intermediate lobe of the pituitary gland of the amphibian Xenopus laevis is under complex neural control. Three neurotransmitters, dopamine, GABA and NPY, coexist in nerve terminals that contact the melanotrope cells. All three neurotransmitters inhibit alpha-MSH release. We have investigated the significance of this neurotransmitter coexistence for the regulation of alpha-MSH release, using an in vitro superfusion system. From experiments where lobes were treated with various combinations of receptor agonists we conclude that the transmitters act in an additive way but have clear, differential actions. Inhibition of secretion by either dopamine, isoguvacine (GABAA receptor agonist) or baclofen (GABAB receptor agonist) occurs rapidly and alpha-MSH secretion rapidly returns when treatment is terminated (recovery from baclofen being relatively fast, that from dopamine relatively slow); in contrast, inhibition by NPY and recovery from NPY-induced inhibition occurs only very slowly. Differential effects of the transmitters were also seen in experiments with 8-bromo-cyclic AMP, which strongly stimulates alpha-MSH secretion from isoguvacine- or baclofen-treated lobes, but is relatively ineffective in stimulating secretion from lobes treated with dopamine or NPY. NPY, furthermore, enables a short phasic stimulation of secretion by isoguvacine and attenuates the inhibitory action of dopamine and baclofen. Altogether it is concluded that the coexisting factors differentially affect the secretory process of the melanotrope cells of Xenopus laevis. NPY has a slow, sustained action whereas dopamine and GABA act fast.
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PMID:Differential effects of coexisting dopamine, GABA and NPY on alpha-MSH secretion from melanotrope cells of Xenopus laevis. 838 12

The acute intraperitoneal administration of anxiolytic diazepam (2 mg/kg) inhibits the activity of the hypothalamic-pituitary-adrenal (HPA) axis, i.e., it decreases the concentration of adrenocorticotropic hormone (ACTH) and corticosterone in female rats. This fall of ACTH and corticosterone levels was reversed by an antagonist of central benzodiazepine receptors-flumazenil. The antagonist of peripheral benzodiazepine receptors-PK 11195, failed to affect diazepam-induced decrement of plasma ACTH and corticosterone levels. The suppressed HPA function obtained after diazepam administration was also antagonized by bicuculline, an antagonist of GABA recognition sites, and by picrotoxin, a drug that blocks the GABA-A receptor associated chloride channel. These results suggest that central benzodiazepine receptors, the part of GABA-A macromolecular complex, are involved in diazepam-induced inhibition of the activity of the HPA axis.
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PMID:Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats. 839 96

The action of met-enkephalin on GABAergic spontaneous miniature IPSPs (smIPSPs) was investigated in CA1 neurons from hippocampal slice cultures. In the presence of excitatory amino acid blockers (2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, DL-2-amino-5-phosphonovaleric acid) and TTX, a continuous high-frequency bombardment of smIPSPs was recorded. The smIPSPs were blocked by the GABAA antagonist bicuculline. The occurrence of the smIPSPs was random and their amplitude distribution was skewed toward larger smIPSPs. Met-enkephalin (10-20 microM) reversibly reduced the frequency and changed the amplitude distribution of the smIPSPs. The proportion of "large" smIPSPs was reduced, but a loss of "small" smIPSPs also contributed to the reduction in smIPSP frequency. The selective mu-receptor agonist DAGO mimicked the effect of met-enkephalin and naloxone blocked the effect of DAGO. Hyperpolarization of the neuronal membranes, produced by reducing the extracellular K+ concentration, did not reduce the frequency of the smIPSPs, nor did it block the effect of DAGO. Reduction of the extracellular concentration of Ca2+ combined with an increase in extracellular Mg2+ or the addition of Cd2+ did not reduce the smIPSP frequency, nor did it block the effect of DAGO. These results suggest that CA1 pyramidal cells of hippocampal organotypic cultures are tonically inhibited by spontaneous release of GABA, through a release mechanism that is independent of propagated sodium action potentials. Met-enkephalin and DAGO reduce the tonic inhibition by reducing the frequency of the smIPSPs, through a direct action on the presynaptic GABAergic terminals. The effect was probably not mediated by hyperpolarization of the presynaptic membrane or by modulation of presynaptic Ca2+ currents.
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PMID:Effects of met-enkephalin on GABAergic spontaneous miniature IPSPs in organotypic slice cultures of the rat hippocampus. 847 86

gamma-Aminobutyric acid (GABA) is the principal depressant neurotransmitter system, but its possible role in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis has not yet been investigated in the dog. Moreover, GABA is one of the factors underlying the syndrome of hepatic encephalopathy (HE), and in dogs with HE, the regulation of the HPA axis is deranged. We have therefore investigated the role of the GABA system in the regulation of the HPC system in 10 healthy dogs and 10 dogs with HE due to congenital portosystemic shunts. The effect of an intravenous injection of the GABA antagonist bicuculline on the release of adrenocorticotropin (ACTH), alpha-melanotropin (MSH), and cortisol was measured in plasma. In healthy dogs, a dose of 1.0 mg/kg caused a marked release of ACTH, MSH, and cortisol, but doses of 0.001 to 0.5 mg/kg produced an inconsistent or no response. The high release of MSH after bicuculline administration indicated that the effect of GABA was predominantly in the neurointermediate lobe of the pituitary. In order to investigate whether the effect of GABA was exerted in the pituitary or at a suprapituitary level, the effect of incubation with GABA on basal and corticotropin-releasing hormone-induced ACTH release was measured in primary cultures of anterior and neurointermediate lobe cells from healthy dogs, and no response was observed. We conclude that in healthy dogs, GABA inhibits the release of ACTH and MSH from the neurointermediate lobe of the pituitary at a suprapituitary level. In dogs with HE, 1.0 mg/kg of bicuculline caused virtually no stimulation of the secretion of ACTH, MSH, or cortisol, indicating deranged GABAergic neurotransmission in HE. This may be explained by an increased GABA tone that prevents the effect of the antagonist. Such a high GABA tone associated with HE has been documented in several other species. Dogs with HE had significantly increased basal levels of ACTH, MSH, and cortisol in plasma, and their cortisol:creatinine ratios in 24-hr urine samples (63 +/- 14.10(-6)) were higher than those of healthy dogs (9 +/- 2.10(-6)). An increased basal HPA activity in dogs with HE is not in agreement with augmented GABAergic inhibition, but this contradiction may be explained by the predominance of effects of dopaminergic disinhibition that has been reported in such dogs.
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PMID:GABAergic inhibition of the pituitary release of adrenocorticotropin and alpha-melanotropin is impaired in dogs with hepatic encephalopathy. 862 16

The nucleus tractus solitarii (NTS), which receives visceral afferent information from the cardiovascular, respiratory, gastrointestinal and taste systems, contains multiple neurotransmitters and neuropeptides throughout its rostral to caudal extent. The neurotransmitters and neuropeptides immunoreactivity is located predominately in varicose fibers and small puncta throughout the neuropil. In addition, immunoreactive NTS neurons for a variety of neurotransmitters and neuropeptides are present in subnuclear regions. The neuroactive substances localized immunohistochemically in the NTS include acetylcholine, the neuropeptides, substance P, methionine- and leucine-enkephalin, beta-endorphin, cholecystokinin, neurotensin, galanin, calcitonin gene-related peptide, somatostatin, FMRMamide, neuropeptide Y, angiotensin II, vasoactive intestinal polypeptide, vasopressin, oxytocin, thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, atrial natriuretic peptide, the catecholamines, dopamine, norepinephrine, epinephrine, serotonin, histamine and the amino acids, GABA and glutamate. The pattern of innervation for each neurotransmitter and neuropeptide is not homogeneously distributed throughout the NTS. Each substance has a unique pattern within the NTS as each subnuclear region contains different immunohistochemical staining patterns and densities of fibers. At the ultrastructural level both neurotransmitters and neuropeptides are present in synaptic terminals that are in contact with different parts of the neuronal membranes. Typically, the labeled terminals contain both small, clear vesicles and large, dense core vesicles with the exception of synaptic terminals containing acetylcholine, GABA and glutamate which do not typically have the large, dense core vesicles. The most frequent post-synaptic target are dendrites and spinous processes. Less frequently, synaptic contacts are present on the cell soma.
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PMID:Immunohistochemical localization of neuropeptides and neurotransmitters in the nucleus solitarius. 867 Jul 16

Rat hypothalamic neurons and endocrine cells from the intermediate lobe of the pituitary were grown in dissociated coculture. Neurons positively stained with an antibody against glutamate decarboxylase established apparent contacts with the alpha-melanocyte-stimulating hormone-positive endocrine cells. These sites of contact were intensely labeled with an antibody against the synaptic protein synapsin I and displayed ultrastructural features characteristic of synapses. Using patch-clamp recordings, we have demonstrated that these contacts correspond to functional GABAergic synapses. The synaptic currents were blocked reversibly by bicuculline (5 microM) and SR95531 (5 microM), two competitive antagonists of the GABAA receptor. At a holding potential of -60 mV, spontaneously occurring IPSCs (s-IPSCs) had small amplitudes (10-100 pA), whereas electrically evoked IPSCs (ee-IPSCs) had amplitudes up to 1 nA. The rise times of both types of IPSCs were fast ( < or = 1 msec), and their decaying phases were fitted in most cases with a single exponential function (time constant 50 msec). The amplitude distribution of s-IPSCs did not reveal clear, equally spaced peaks and was little affected by tetrodotoxin, suggesting that most s-IPSCs were miniature IPSCs. Reduction of extracellular calcium concentration to 0.3 mM induced a marked decrease in s-IPSC frequency and revealed a single amplitude peak at 10 pA, suggesting that a single quantum of GABA activates 8-10 GABAA channels. Thus, our preparation might be an interesting model to study different aspects of synapse formation between a central neuron and its target as well as the fundamental mechanisms of synaptic transmission at central synapses.
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PMID:Characterization of functional GABAergic synapses formed between rat hypothalamic neurons and pituitary intermediate lobe cells in coculture: Ca2+ dependence of spontaneous IPSCs. 875 16

Prenatally stressed (PS) human infants and experimental animals show attentional deficits, hyperanxiety and disturbed social behavior. Impaired coping in stressful situations in adult PS monkeys and rodents is associated with dysregulation of the HPA axis, characterized by decreased feedback inhibition of corticotropin-releasing hormone (CRH) and prolonged elevation of plasma glucocorticoids in response to stress. PS rats have higher levels of CRH in the amygdala, fewer hippocampal glucocorticoid receptors and less endogenous opioid and GABA/BDZ (benzodiazepine) inhibitory activity. The mechanisms by which maternal stress induce these long-lasting changes in the developing fetal neuroaxis remain to be elucidated. It is suggested that impaired coping in stressful situations and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, result from the action of maternal hormones released during stress on the developing fetus. The similarities in coping behavior and dysregulation of the HPA axis in PS animals to those in humans with depression, suggest that gestational stress, at a critical time during fetal development, may increase the propensity to develop this condition.
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PMID:Does prenatal stress impair coping and regulation of hypothalamic-pituitary-adrenal axis? 899 5

The amphibian Xenopus laevis adapts the colour of its skin to the colour of its background, by the release of the pro-opiomelanocortin-derived peptide alpha-melanophore-stimulating hormone from the pars intermedia of the pituitary gland. Suprachiasmatic neurons play an important role in adaptation to a light background as they produce the neurotransmitters GABA, dopamine and neuropeptide Y, which inhibit the release of alpha-melanophore-stimulating hormone. These factors are transported to axon varicosities contacting the melanotrope cells. In these varicosities GABA resides in electron-lucent vesicles and neuropeptide Y and dopamine coexist in electron-dense vesicles. In this study the effects of background adaptation on the morphology of the varicosities in the pars intermedia were studied, using immunoelectron microscopy and morphometry with freeze-substitution-fixed material. Varicosities were found singly and in clusters throughout the pars intermedia. Varicosities were identified by the presence of electron-dense and electron-lucent secretory vesicles, the latter being immunopositive for anti-GABA. Both varicosity types revealed active zones with exclusively GABA-containing vesicles in contact with the presynaptic membrane. When white- and black-adapted animals were compared, significant background effects were found with respect to the organization of the varicosities: the density of varicosity profiles was twice as high in white-adapted animals as in black-adapted ones, due to an increase in density of the clustered varicosities. Furthermore, in white-adapted animals varicosities were about twice as large as in black-adapted animals. With respect to vesicle types, single and clustered varicosities showed a differential effect. For both the population of electron-lucent and electron-dense vesicles, single varicosities showed equal numbers in white- and black-adapted animals, but clustered varicosities showed higher numbers of electron-lucent and electron-dense vesicles in black-adapted animals, indicating storage of neurotransmitters. Finally, in varicosities of white-adapted animals the number and size of the active zones and the number of electron-lucent vesicles attached to the active zones, were about twice as high as in black-adapted animals, indicating a stronger GABA release. It is concluded that the profound effects of environmental light conditions on synaptic structure and substructure in the Xenopus pars intermedia are related to a changed release activity of neurotransmitters inhibiting the activity of the melanotrope cells.
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PMID:Background adaptation and synapse plasticity in the pars intermedia of Xenopus laevis. 904 93

Stressful experience during early brain development has been shown to produce profound alterations in several mechanisms of adaptation, while several signs of behavioral and neuroendocrine impairment resulting from neonatal exposure to stress resemble symptoms of dysregulation associated with major depression. This study demonstrates that when applied concomitantly with the stressful challenge, the steroid GABA(A) receptor agonist 3,21-dihydropregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) can attenuate the behavioral and neuroendocrine consequences of repeated maternal separation during early life, e.g., increased anxiety, an exaggerated adrenocortical secretory response to stress, impaired responsiveness to glucocorticoid feedback, and altered transcription of the genes encoding corticotropin-releasing hormone (CRH) in the hypothalamus and glucocorticoid receptors in the hippocampus. These data indicate that neuroactive steroid derivatives with GABA-agonistic properties may exert persisting stress-protective effects in the developing brain, and may form the basis for therapeutic agents which have the potential to prevent mental disorders resulting from adverse experience during neonatal life.
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PMID:Neonatal treatment of rats with the neuroactive steroid tetrahydrodeoxycorticosterone (THDOC) abolishes the behavioral and neuroendocrine consequences of adverse early life events. 906 54

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


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