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 binding characteristics of histogranin (HN), an endogenous peptide first recognized for its antagonism of N-methyl-D-aspartate (NMDA) responses, were determined in membrane preparations of rat brain. [125I][Ser1]HN, a stable bioactive analog of HN, bound specifically and reversibly to a homogenous population of high-affinity sites with a Kd of 25 nM and a Bmax of 410 fmol/mg protein. The binding of [125I][Ser1]HN increased linearly with membrane protein concentration and was destroyed upon membrane pretreatment with trypsin. The binding displayed rapid association and dissociation kinetics and was blocked by peptides possessing close homology with HN in the following order: [Ser1]HN-(1-15) > HN > [Ser1]HN-(1-14) > HN-(2-15) > [Ser1]-HN-(1-10) > HN-(6-10). Unrelated peptides such as substance P, beta-endorphin, neuropeptide Y, [Met5]enkephalin, [Leu5]enkephalin, dynorphin A(1-13) and neuromedin C were inactive in competition binding assays against [125I]Ser1]HN. Ligands of the binding domains of the NMDA receptor, such as (+)3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, (+) 5-methyl-10,11-dihydro 5H-dibenzo[a, d]cyclohepten-5,10-imine hydrogen maleate, 1-N-(2-thienyl)cyclohexylpiperidine, glycine and glutamate were also ineffective in competing for [125I][Ser1]HN binding sites. Interestingly, specific ligands for the polyamine site on the NMDA receptor, as well as the cations Mg++ and Zn++ inhibited [125I][Ser1]HN binding. The polyamine antagonist diethylenetriamine produced a noncompetitive inhibition with an IC50 (175 nM) comparable to that of HN (75 nM). The cations Zn++ and Mg++ displaced [125I][Ser1]HN binding with IC50 values of 18 and 240 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterization of [125I][Ser1]histogranin binding sites in rat brain. 822 61

This review of the CNS effects of the neurohypophyseal hormones and related neuropeptides discusses recent data illustrating the significance of these principles in brain function, synthesis, distribution, in particular in extrahypothalamic brain structures, binding sites, and signal transduction. Binding sites for vasopressin of the vascular V1a type have been found in the CNS and there is evidence for the existence of a subtype of the antidiuretic V2 receptor in the brain. Also two types of oxytocin binding sites have been detected. One widely distributed throughout the CNS is comparable to the uterine type receptor and a sexually dimorphic slightly different type is found in the ventromedial nucleus. Vasopressin and oxytocin can be converted to highly selective C-terminal fragments as AVP-(4-9) and OXT-(4-9) and shorter fragments. Conversely they can be acetylated. This almost completely blocks intrinsic activity in bioassays for central and peripheral effects. Such modifications are a good example of the plasticity of a neuropeptide system. For a number of CNS effects of the neurohypophyseal hormones, the whole molecule is required, as it is for their endocrine effects. This is the case for the influence of vasopressin on social communication, temperature regulation, epilepsy, and barrel rotation which may be an animal model of febrile convulsions, and some aspects of the central regulation of the cardiovascular system and for oxytocin on sexual behavior, social communication, and grooming. Nonendocrine C-terminal conversion products seem to exert their effects exclusively on the brain. These neuropeptides modulate learning and memory processes, social recognition, and rewarded behavior. The neuroendocrine and neuropeptide effect of vasopressin and oxytocin and related neuropeptides often exert their CNS effects in an opposite way. Neurochemical and electrophysiological studies suggest that norepinephrine, dopamine, serotonin, and glutamate are the neurotransmitters involved in the influence of the neurohypophyseal hormones and related neuropeptides on brain function. It appears that adequate amounts of vasopressin and oxytocin to induce these effects are released at the appropriate sites of action. It is postulated that the mix of neuropeptides released in the brain in response to environmental changes qualifies the behavioral, neuroendocrine, and immune response and the response of the autonomic nervous and vegetative systems of the organism. Although various other neuropeptides, such as those colocalized in vasopressinergic and oxytocinergic neurons, those produced in pro-opiomelanocortin (POMC) systems, and others, play a role in the modulation of adaptive responses, the neurohypophyseal hormones are unique in that their production sites in the hypothalamus serve the periphery, the pituitary, and the brain.
 ...
PMID:Central nervous system effects of the neurohypophyseal hormones and related peptides. 825 77

The present study determined whether interleukin-2 (IL-2) and IL-2 receptors are present in the adult rat hypothalamus. In addition, we determined whether IL-2 is involved in the regulation of neurotransmitter release from hypothalamic slices. In the hypothalamus, the highest levels of endogenous IL-2 and IL-2 receptors were localized to the median eminence and arcuate nucleus. Application of exogenous IL-2 to hypothalamic slices produced significant decreases of potassium (25 mM)-evoked [3H]noradrenaline release (24%) without significantly affecting the evoked release of [14C]glutamate, [14C]5-hydroxytryptamine, [3H]dopamine or [3H] gamma-amino butyric acid. In addition, IL-2 increased the potassium-evoked release of methionine-enkephalin (by 78%) and beta-endorphin (by 38%) from hypothalamic slices without affecting the release of leucine-enkephalin. In contrast, the spontaneous release of neurotransmitters and neuropeptides was not affected by exogenous IL-2. Overall, the findings of this study suggest that hypothalamic IL-2 is an endogenous neurokine that may be of consequence to the regulation of hypothalamic function.
 ...
PMID:Interleukin-2 regulates monoamine and opioid peptide release from the hypothalamus. 847 53

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.
 ...
PMID:Immunohistochemical localization of neuropeptides and neurotransmitters in the nucleus solitarius. 867 Jul 16

Intact adult male rats fed an alcohol [ethanol (EtOH)] diet for 10 days show blunted adrenocorticotropic hormone (ACTH) release in response to immune signals such as the cytokine interleukin-1 beta (IL-1 beta) and endotoxin [lipopolysaccharide (LPS)], as well as to physical stress (mild electroshocks). The mechanisms responsible for this effect remain poorly understood, but we have recently reported that decreased pituitary responsiveness to vasopressin (VP) might play a role. In naive rats, nitric oxide (NO) exerts a restraining influence on the response of the hypothalamic-pituitary (H-P) axis to cytokines and VP. The ability of long-term EtOH treatment to increase glutamate receptors, and thus NO formation, prompted us to test the hypothesis that abnormally high NO concentrations might modulate the influence of the drug. Blockade of the activity of NO synthase (NOS), the enzyme responsible for NO formation, with the arginine derivative L-N omega nitro-L-arginine-methylester (L-NAME), augmented the ACTH response to IL-1 beta or LPS in both control (C) and EtOH-fed (E) rats. Indeed, after L-NAME treatment, ACTH concentrations were statistically comparable in C and E animals injected with endotoxin or a large dose of IL-1 beta. VP-induced ACTH secretion also became comparable in both experimental groups after blockade of NOS activity. In contrast, the decreased response of the H-P axis of E animals to shocks was only slightly ameliorated, compared with that of C rats. It is therefore possible that changes in the NOergic tone induced by alcohol play a role in the decreased response of the H-P axis to cytokines, possibly in part by altering the stimulatory action of VP on the corticotrophs. On the other hand, in E rats NO seems to exert only a minimal influence on the central nervous system circuits activated by shocks.
 ...
PMID:Adult male rats exposed to an alcohol diet exhibit a blunted adrenocorticotropic hormone response to immune or physical stress: possible role of nitric oxide. 874 13

A neutral endopeptidase (NEP) from Lactococcus lactis has recently been cloned and shown to contain high sequence homology with the human neutral endopeptidase, endopeptidase 24.11 (I. Mierau et al., J. Bacteriol. 175, 2087-2096, 1993). The gene for the neutral endopeptidase from L. lactis was cloned into the pQE expression vector, resulting in the fusion of a hexahistidine at the N-terminus. The recombinant enzyme was expressed to high levels in Escherichia coli (approximately 10 mg/liter of culture) and purified to homogeneity in a two-step procedure. A number of peptides were studied as substrates for the enzyme. The enzyme cleaves the following peptides at the Gly3-Phe4 bond: enkephalins, dynorphins A-6, A-8, A-9, A-10, A-13, and A-17, and alpha-neo-endorphin. In addition the enzyme hydrolyzes bradykinin, substance P, beta-endorphin, ACTH, and VIP. Although the cleavage patterns observed are similar to that seen with mammalian neutral endopeptidase, the lactococcal enzyme more efficiently cleaves larger peptide substrates. As observed with the mammalian neutral endopeptidase, the lactococcal enzyme exhibits higher kcat/K(m) values for the enkephalins than for their corresponding amides, indicating the functionality of an active-site arginine. Inactivation of the lactococcal endopeptidase by diethyl pyrocarbonate and protection afforded by the substrate dynorphin A-6 indicate the functionality of a positionally conserved active-site histidine. This was confirmed by demonstrating that conversion of this histidine, histidine 587, to glutamine generated inactive enzyme. Similarly, conversion of the putative zinc ligand glutamate 535 to glutamine led to inactive enzyme. These studies indicate a conservation of critical catalytic residues between the two enzymes and suggest that the lactococcal endopeptidase is a better model than thermolysin for the mammalian enzyme.
 ...
PMID:Heterologous expression and characterization of recombinant Lactococcus lactis neutral endopeptidase (neprilysin). 880 62

Neonatal treatment with monosodium glutamate (MSG) decreases proopiomelanocortin (POMC) peptides and results in obesity. The yellow mouse is a model of obesity induced by the viable yellow (Avy) gene at the agouti locus on Chromosome 2, which results in overproduction of a POMC receptor antagonist. Thus we hypothesized that MSG, when imposed on the genetically susceptible model, would alter the development of obesity. Both yellow obese (Avy) and black lean (alpha/alpha) males were injected on Postnatal Days 1, 3, 5, 7, and 9 with 2.0 mg/g body weight MSG or saline SC. Their food intake, growth parameters, and neurochemical status were examined. Paradoxically, MSG interacted with the yellow phenotype to delay the rapid rate of weight gain characteristic of this model (p < 0.05). Food intake was decreased (p < 0.05) in both phenotypes treated with MSG, as was hypothalamic content of dopamine (p < 0.05) and of the POMC peptide, beta-endorphin (p < 0.001). The yellow obese phenotype was more sensitive than the black lean phenotype to the neurochemical effect of early postnatal MSG administration. Recent reports suggest the agouti locus protein is an antagonist of the receptor for another POMC peptide, melanocyte-stimulating hormone (MSH). Therefore, the balance of functional activity between various POMC peptides appears to be an important factor in the development of both acquired and genetic obesity.
 ...
PMID:Neonatal MSG reduces hypothalamic DA, beta-endorphin, and delays weight gain in genetically obese (A viable yellow/alpha) mice. 880 53

The release of catecholamines and cortisol from the perifused adrenal region and caudal vein of the eel (Anguilla rostrata) was compared with the release of 39 amino acids and related compounds. Dopamine, norepinephrine and epinephrine were present in all perifusates of the adrenal region. Dopamine release from the caudal vein exceeded that from the adrenal region, and norepinephrine and epinephrine were not detected. Cortisol was present in the perifusate of the adrenal region but virtually absent in caudal vein perifusate. Of the six substances with known or suspected neurotransmitter function, taurine, aspartate, glutamate, glycine and alanine were present in all or almost all samples from both the adrenal equivalent and the caudal vein. gamma-aminobutyric acid (GABA) was detected in a few samples from either preparation. The release of taurine and phosphoethanolamine may be linked to that of norepinephrine and epinephrine. Adrenocorticotropic hormone (ACTH) enhanced the release of cortisol, aspartate, valine, leucine and ornithine from the adrenal region, but the release appears to be from differing sources or cellular pools. Overall, the study revealed that both the adrenal region and caudal vein release a large number of amino acids and related substances. The caudal vein, and possibly other blood vessels as well, may be a major source of circulating dopamine.
 ...
PMID:Release of amino acids and related compounds from the adrenal equivalent and caudal vein of the eel in vitro. 883 79

We have recently demonstrated that a single administration of m-chlorophenylpiperazine (m-CPP, a preferential 5-HT2C receptor agonist) produces tolerance to its stimulatory effect on adrenocorticotropic hormone (ACTH) concentrations when challenged 24 h later with the same dose of m-CPP. In the present study, we studied the effects of pretreatment with various N-methyl-D-aspartate (NMDA) receptor antagonists on development of tolerance to m-CPP's stimulatory effect on ACTH concentrations. Pretreatment with various NMDA receptor antagonists such as 5.7-dichlorokynurenic acid (1.0 mg/kg), 3-amino-1-hydroxy 2-pyrrolidone (1.0 mg/kg), dizocilpine (0.1 mg/kg) and ifenprodil (1.0 mg/kg) injected 30 min before the first injection of m-CPP (2.5 mg/kg) blocked development of tolerance to m-CPP's stimulatory effect on ACTH concentrations in rats injected 24 h later with the same dose (2.5 mg/kg) of m-CPP. These findings suggest that tolerance to postsynaptic 5-HT2C receptor-mediated response is initiated though stimulation of NMDA receptor complex and, furthermore, demonstrate a functional interaction between the 5-HT and glutamate systems.
 ...
PMID:NMDA receptor antagonists block development of tolerance to m-CPP-induced increases in ACTH concentrations in rats. 885 8

Dopaminergic hyperactivity in nucleus accumbens and dopaminergic hypoactivity in prefrontal cortex are thought to underlie positive and negative symptoms of schizophrenia, respectively. The caudate putamen is the neuroanatomical substrate for extrapyramidal side effects resulting from chronic antipsychotic treatment. We sought to identify potential endogenous regulators of dopamine release that might produce differential effects in these brain areas. We tested neurotensin, N-acetyl-aspartyl-glutamate and beta-endorphin for potential regulation of [3H]dopamine release in these regions of guinea pig brain. All three peptides stimulated dopamine release, above basal activity, at all concentrations tested in the three regions. Neurotensin significantly enhanced and N-acetyl-aspartyl-glutamate had no significant effect on N-methyl-D-aspartate-stimulated release from all three regions. In contrast, beta-endorphin significantly inhibited N-methyl-D-aspartate-stimulated release in nucleus accumbens and caudate putamen. These results suggest that these neuropeptides may regulate endogenous dopamine release and therefore may be potential therapeutic targets for antipsychotic drug development.
 ...
PMID:Neurotensin, N-acetyl-aspartylglutamate and beta-endorphin modulate [3H]dopamine release from guinea pig nucleus accumbens, prefrontal cortex and caudate-putamen. 892 14


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