Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The observation that opiates and endorphins exert euphorogenic effects in normal probands points to a possible involvement of endorphins in different types of affective disorders. There are several powerful arguments that the activation of particular central opiate receptors (e.g. by "opium cure", beta-endorphin, partial agonists, release of endorphins via electroconvulsion) exerts curative effects in endogenous depression. Results from a double-blind investigation of the possible antidepressant action of the opiate partial agonist buprenorphine in patients with endogenous depression revealed a strong antidepressant effect of this substance. A series of anticonvulsants, possibly acting via a GABA-ergic-like mechanism (valproate, dipropylacetamide, carbamazepine and oxcarbazepine), have recently been shown by different groups to possess antimanic and also, partially, antidepressant properties. Furthermore, a synergistic mode of action in the prophylaxis of manic episodes has been observed as concerns valproate and lithium. On the other hand, there is some evidence from both in vitro and in vivo animal experiments that chronic application of lithium results in a modification of the GABA-turnover. The present paper reviews the present state of knowledge concerning the concept of a GABA-dependent regulation of affective states.
 ...
PMID:Current perspectives in the pharmacopsychiatry of depression and mania. 630 56

The proconvulsant actions of high doses of systemic morphine are probably mediated by 3 different systems. One of them produces non-convulsant electrographic seizures and can be activated separately from the others both by intracerebroventricular injections as well as microinjections into discrete subcortical areas. The enkephalins and beta-endorphin, when administered to the same loci, produce similar effects. Pharmacological evidence suggests that specific opiate receptors of the delta-subtype mediate the epileptiform effects produced by this system. The second system mediating proconvulsant effects of systemic morphine is not mediated by stereo-specific opiate receptors. It produces behavioral convulsions, and the GABA-ergic system has been implicated in its action. A third proconvulsant action of systemic morphine can be activated separately from the other two systems by administering this compound with other convulsive agents or manipulations. Specific mu-type opiate receptors are implicated in this effect. In addition to potent proconvulsant effects, systemic morphine also has anticonvulsant properties which are mediated by specific opiate mu-receptors. The conditions under which morphine acts as a proconvulsant rather than an anticonvulsant agent are, as yet, not understood.
 ...
PMID:Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems. 631 87

Opioid peptide-like (OPL)-immunoreactivity and (the GABA-biosynthetic enzyme) glutamic acid decarboxylase-like (GAD)-immunoreactivity were localized in rat neostriatum and central amygdaloid nucleus (ACE) using a polyclonal sheep antiserum to rat brain GAD and a monoclonal mouse antibody to the N-terminus of beta-endorphin (3-E7) as primary antisera. PAP-immunohistochemistry revealed GAD-immunoreactivity in the majority of neurons in neostriatum and ACE. OPL-immunoreactivity was observed in numerous neurons in ACE, but only in few neostriatal nerve cells. In double immunofluorescence in the same section OPL- and GAD-immunoreactivity colocalized in few medium size cells in the neostriatum, but in numerous neurons in ACE. The existence of opioid peptide containing GABAergic neurons in ACE and neostriatum is demonstrated.
 ...
PMID:Opioid peptide-like immunoreactivity localized in GABAErgic neurons of rat neostriatum and central amygdaloid nucleus. 666 48

Huntington's Disease (HD) is a progressive degenerative disorder of the central nervous system inherited as an autosomal dominant trait. Clinically, the disorder is characterized by choreoathetosis (with age of onset typically in the late thirties or early forties) and neuropsychiatric disturbance. The striatum is particularly vulnerable to the degenerative disease process, with selective loss of medium spiny neurons and decreased levels of associated neurotransmitters, including substance P. GABA, met-enkephalin and dynorphin. Although the underlying pathophysiology is unknown, recent theories concerning pathogenesis have involved mitochondrial abnormalities and excitotoxin-mediated damage. The gene for HD has recently been discovered and characterized as an unstable CAG trinucleotide repeat sequence on the short arm of chromosome 4 (now known as IT15). The direct test now available for the HD gene has facilitated disease diagnosis, particularly for those with unclear family history or chorea of uncertain origin; presymptomatic testing is also available. Management of affected individuals is unsatisfactory as only symptomatic control is available. However, as the effect of the genetic abnormality may soon be known, specific treatment of the disorder may become available in the near future.
 ...
PMID:Huntington's disease: recent advances in diagnosis and management. 775 74

Our research focusses on the role of brain and hypophysis in the control of background adaptation in the clawed toad, Xenopus laevis. This adaptation is regulated by alpha-melanophorestimulating hormone (alpha-MSH). Previously, it was shown that various neurotransmitters influence alpha-MSH release. Here we report about the origin of these factors. Using retrograde labelling techniques combined with immunocytochemistry, it was found that the inhibitory transmitters dopamine and neuropeptide Y coexist in neurons in the suprachiasmatic nucleus. These neurons project to the pars intermedia and synaptically contact the alpha-MSH-producing melanotrope cells. In the synapses also GABA is present. Tracing of the optic nerve indicated the presence of a direct retinosuprachiasmatic tract. Furthermore, locus coeruleus neurons project to the pars intermedia. They contain the inhibitory transmitter noradrenaline. The stimulatory factors corticotropin-releasing hormone and thyrotropin stimulating hormone originate from the magnocellular nucleus which send its processes to the neural lobe of the hypophysis.
 ...
PMID:Central control of melanotrope cells of Xenopus laevis. 780 85

The ring-A-reduced progesterone derivative 5 alpha-pregnan-3 alpha-ol-20-one (tetrahydroprogesterone) is synthesized under normal physiological conditions in the brain and is a potent modulator of the GABA receptor. This neurosteroid has significant sedative and anxiolytic properties. Corticotropin-releasing hormone plays a major role in stress-induced activation of the hypothalamo-pituitary-adrenal axis, and sustained hyperactivity of hypothalamic corticotropin-releasing hormone-producing neurons may be causally related to both, increased pituitary-adrenal secretion and behavioural symptoms observed in anxiety and affective disorders. We investigated the effect of tetrahydroprogesterone on corticotropin-releasing hormone-induced anxiety, the basal and methoxamine-stimulated release of corticotropin-releasing hormone from hypothalamic organ explants in vitro, and adrenalectomy-induced up-regulation of the gene expression of corticotropin-releasing hormone in the hypothalamic paraventricular nucleus in rats. At doses of 5 and 10 micrograms i.c.v., tetrahydroprogesterone counteracted the anxiogenic action of 0.5 microgram of corticotropin-releasing hormone. Tetrahydroprogesterone did not alter the basal release of corticotropin-releasing hormone in vitro, but suppressed the stimulatory effect of the alpha 1-adrenergic agonist methoxamine on this parameter. Measurements of the steady-state levels of mRNA coding for corticotropin-releasing hormone by quantitative in situ-hybridization histochemistry revealed that tetrahydroprogesterone was equipotent with corticosterone in preventing adrenalectomy-induced up-regulation of peptide gene expression. Systemic administration of tetrahydroprogesterone also restrained adrenalectomy-induced thymus enlargement. These results demonstrate that tetrahydroprogesterone has anxiolytic effects that are mediated through interactions with hypothalamic corticotropin-releasing hormone in both, genomic and non-genomic fashions.
 ...
PMID:The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus. 781 4

Corticotropin releasing factor (CRF) is a 41 amino acid peptide implicated in the expression of stress- and fear-enhanced behaviors. CRF potentiates the amplitude of the startle reflex, and this effect is reversed by benzodiazepines (BDZ), suggesting that the startle-enhancing effects of CRF are modulated by changes in the GABA/BDZ receptor complex. In the present study, CRF-potentiated startle is inhibited by alphaxalone, a pregnane steroid anesthetic that is thought to act via the GABA/BDZ receptor complex. Alphaxalone (ALX) does not reduce CRF-potentiated startle by producing a generalized reduction in reactivity, since blockade of CRF-stimulated startle was not accompanied by an ALX-induced reduction in baseline startle amplitude and ALX does not reduce strychnine-potentiated startle. The effects of alphaxalone on CRF-potentiated startle may not be generalized to all CRF-stimulated behaviours, since alphaxalone failed to disrupt CRF-stimulated locomotor activity. CRF-potentiated startle is a useful assay for studying the effects of novel anxiolytic agents, and alphaxalone appears to be a steroid anesthetic with anxiolytic properties in this assay.
 ...
PMID:Alphaxalone, a steroid anesthetic, inhibits the startle-enhancing effects of corticotropin releasing factor, but not strychnine. 786 86

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.
 ...
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.
 ...
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.
 ...
PMID:Effects of met-enkephalin on GABAergic spontaneous miniature IPSPs in organotypic slice cultures of the rat hippocampus. 847 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>