Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deficiency in the secretion of luteinizing hormone-releasing hormone (LHRH) from the median eminence (ME) is one of the factors limiting reinitiation of estrous cycles following parturition in cows. In previous studies, administration of naloxone, an opioid receptor antagonist, to postpartum cows increased LH secretion, suggesting that endogenous opioids inhibit the secretion of LHRH. This study employs quantitative light microscopy to describe morphological changes in the distribution of immunoreactive beta-endorphin (ir-beta-END) neurons in the hypothalamus of anestrous early postpartum (EPP, days 10-16, n = 5), midpostpartum (MPP, days 33-43, n = 4) and multiparous cycling cows (CYC, months 12-14, n = 4). Cryostat sections (60 microns) of perfusion-fixed ventral diencephalon and forebrain were immunostained with anti-beta-END serum via the biotin-avidin-peroxidase method or double stained sequentially with anti-LHRH serum, then anti-beta-END serum. In all cows, beta-END immunoreactive perikarya, mostly bipolar neurons, were located in the arcuate and periarcuate nucleus (ARC), with some perikarya in the ME. Within the ARC, the percentage area immunostained for ir-beta-END was greater (p < 0.01) for the CYC than EPP cows, with MPP intermediate but not significantly different from the other groups. Consistent for all cows, the percentage area of ir-beta-END in ventral ARC regions was greater (p < 0.05) than dorsal ARC regions. Fibers from these neurons coursed into the anterior hypothalamus, preoptic area and bed nucleus of stria terminalis. Ventrally projecting fibers entered the ME forming a densely staining band within the external layer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distribution of beta-endorphin immunoreactivity in the arcuate nucleus and median eminence of postpartum anestrus and luteal phase cows. 143 81

In cultured human umbilical vein endothelial cells, 5-HT and alpha-methyl 5-HT stimulated [45Ca2+] uptake in concentration-dependent manner, whereas the 5-HT1 agonists, m-CPP (1-(3-chlorophenyl)piperazine and 2-MPP (1-(2-methoxyphenyl)piperazine), were without effect. In turn, 5-HT-stimulated [45Ca2+] uptake was inhibited in concentration-dependent manners by the 5-HT receptor antagonists ketanserin (5-HT2), LY 53,857 (5-HT2) and methiothepine (5-HT1/2) and to a lesser degeree by MDL 72222 (5-HT3) and BRL 43694 (5-HT3) whereas (+/-)-propranolol (5-HT1) was without effect. These data indicate that 5-HT stimulates Ca2+ uptake by endothelial cells via activation of a 5-HT2 receptor subtype. 5-HT was without effect on de novo prostacyclin (PGI2) synthesis over the concentration of 5-HT that elicited [45Ca2+] uptake. Since 5-HT did not stimulate PGI2, an event associated with an increase in levels of intracellular Ca2+, it is postulated that the uptake of 45Ca2+ reflects changes of Ca2+ at the level of the plasma membrane rather than on intracellular changes. 5-HT-stimulated Ca2+ uptake may be of relevance to endothelium-dependent relaxation, vascular permeability and endothelial repair and proliferation.
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PMID:5-Hydroxytryptamine stimulates 45Ca2+ uptake by human umbilical vein endothelial cells in culture: mediation by 5-HT2 receptor subtypes. 151 43

Recent progress is summarized on the mechanism of phototransduction by sensory rhodopsin I (SR-I), a phototaxis receptor in Halobacterium halobium. Two aspects are emphasized: (i) The coupling of retinal isomerization to protein conformational changes. Retinal analogs have been used to probe chromophore-apoprotein interactions during the receptor activation process. One of the most important results is the finding of a steric trigger deriving from the interaction of residues on the protein with a methyl group near the isomerizing bond of the retinal (at carbon 13). Recent work on molecular genetic methods to further probe structure/function includes the synthesis and expression of an SR-I apoprotein gene designed for residue replacements by cassette mutagenesis, and transformation of an H. halobium mutant lacking all retinylidene proteins known in this species to SR-I+ and bacteriorhodopsin (BR)+. (ii) The relay of the SR-I signal to a post-receptor component. A carboxylmethylated protein ("MPP-I") associated with SR-I and found in the H. halobium membrane exhibits homology with the signaling domain of eubacterial chemotaxis transducers (e.g., Escherichia coli Tar, Tsr, and Trg proteins), suggesting a model based on SR-I----MPP-I signal relay.
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PMID:Sensory rhodopsin I: receptor activation and signal relay. 152 61

Previous studies from this laboratory demonstrated that (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, did not prevent neurotoxicity to dopaminergic neurons in mice produced by systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, Turski et al. [Nature 349, 414-418 (1991)] reported that extended treatment of rats with NMDA receptor antagonists (six injections at 4-h intervals) did prevent the loss of nigral dopaminergic neurons resulting from an intranigral infusion of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of MPTP. The present studies examined if a similar extended treatment with MK-801 would protect mice from the neurotoxicity of systemically administered MPTP. Six intraperitoneal injections of MK-801 given at 4-h intervals did not protect mice against the MPTP-induced neostriatal dopamine loss measured 1 week after treatment. In other experiments, designed to replicate and expand on the results of Turski et al. (1991), the extended treatment of rats with MK-801 did not prevent MPP(+)-induced cell loss in the infused substantia nigra pars compacta or the dopamine depletion in the ipsilateral neostriatum at 7-11 days after MPP+ infusion. These results do not support the hypothesis that NMDA receptors are involved with MPTP/MPP(+)-induced neurodegeneration.
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PMID:MK-801 fails to protect against the dopaminergic neuropathology produced by systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice or intranigral 1-methyl-4-phenylpyridinium in rats. 156 Feb 47

The conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to its toxic 1-methyl-4-phenylpyridinium (MPP+) metabolite catalyzed by monoamine oxidase (MAO) type B is likely to occur within glial cells in the central nervous system. In this study, primary cultures of mouse astrocytes were used to assess the biochemical and toxic consequences of exposure to MPTP. MPTP caused a concentration-dependent loss of cell viability. This effect was probably due to the intracellular generation of MPP+, because cytotoxicity was prevented by preincubation of astrocytes in the presence of MAO inhibitors. After addition of 250 microM MPTP, loss of cell viability was preceded by an increased rate of glucose utilization and lactate accumulation, and by depletion of ATP. The ratio between the rates of lactate production (0.37 mM/hr) and glucose consumption (0.2 mM/hr) was 1.85, indicating that most of the glucose present in the medium was stoichiometrically converted to lactate via glycolysis. A remarkable correlation was found between ATP depletion and cytotoxicity caused by MPTP, and, when astrocytes were incubated in glucose-free medium, both ATP depletion and loss of viability occurred more rapidly. Finally, even after exposure for several days, astrocyte death could be prevented by washing MPTP from the incubation medium, suggesting that MPP(+)-induced mitochondrial damage may be reversible. We conclude that prolonged exposure of astrocytes to MPTP may result in loss of viability via the MAO-dependent generation of MPP+ and the ability of this toxic metabolite to impair mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in primary cultures of mouse astrocytes. 156 Mar 84

Deficiency in secretion of luteinizing hormone releasing hormone (LHRH) from the median eminence (ME) is one of the factors limiting reinitiation of estrous cycles following parturition in cows. This study employs quantitative light microscopy to describe morphological changes in LHRH neurons obtained from cows at three postpartum times. Tissues were obtained from anestrous early postpartum (EPP; days 10-16, n = 5), midpostpartum (MPP; days 33-43, n = 4), and multiparous cycling (CYC; months 12-14, n = 4) cows. Following perfusion fixation, cryostat sections (60 microns) of the ventral forebrain were immunostained with anti-LHRH serum via the biotin-avidin-peroxidase method. In all cows, LHRH perikarya formed a loosely arranged continuum, extending from anterior to posterior within the diagonal band of Broca, the lateral and medical preoptic areas, and the anterior hypothalamus. Width and length of perikarya were similar between postpartum groups. The number of dendrite-like processes per neuron (p less than 0.01) and average or total length of process per neuron (p less than 0.001) were greater in the CYC than in the EPP and MPP cows. Although all groups of cows contained a spectrum of lengths of dendrite-like processes, both EPP and MPP cows obtained a greater (p less than 0.05) percentage of neurons with shorter processes and a smaller percentage of neurons with longer processes. Within the ME, the percentage area occupied by immunostained fibers was less (p less than 0.05) in EPP cows than in MPP or CYC cows.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphological differences among luteinizing hormone releasing hormone neurons from postpartum and estrous cycling cows. 156 5

Immunoassays sensitive to a broad range of compounds structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) and 1-methyl-4-phenylpyridine (MPP+) have been developed and used to test for the presence of possible chemically related neurotoxins in the brains of Parkinson's disease patients. The sensitivity and chemical reactivity of the polyclonal antibodies used in these assays have been characterized with a range of endogenous and chemically related materials. Two methods were developed and tested for extraction followed by chromatographic separation which would be applicable to stored or accumulated substances. The immunoassays were tested and applied to the assay of tissue extracts from MPTP or MPTP-analogue exposed animals, and indicated detectability of MPP(+)-immunoreactivity greater than 8 weeks after exposure to MPTP in monkey brain. No difference in immunoactivity was measured in extracts from human brains of Parkinson's disease patients or controls, and particularly low levels of immunoreactivity were found in the striatum relative to the levels measured in several cortical regions. From these studies, there is no evidence for the role of an environmental neurotoxin chemically related to MPTP in the pathogenesis of Parkinson's disease.
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PMID:Search for neurotoxins structurally related to 1-methyl-4-phenylpyridine (MPP+) in the pathogenesis of Parkinson's disease. 157 86

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), the active product of MPTP, caused Parkinson's disease-like symptoms. The mechanism of action of MPP+ is unknown, but analogues of MPTP lacking an N-methyl group were found to be essentially devoid of toxicity, which means that the methyl group of the pyridine ring plays a role in the toxicity. This is of interest because S-adenosylmethionine (SAM), which is the biologic methyl donor and requires a methyl group for its action, also caused MPP(+)-like motor deficits in rodents. Therefore, the requirement of a methyl group by MPTP and MPP+ for their actions suggests that, like SAM, MPP+ and MPTP may serve as methyl donors. This hypothesis was tested by reacting SAM, MPP+, or MPTP with dopamine in the presence of catechol-O-methyltransferase and measuring the methylated product of dopamine produced. Like SAM, MPP+, but not MPTP, methylated dopamine. The methylated product coeluted from chromatographic columns with standard 3-methoxytyramine. Concentrations of 15.6, 62.5, 250, and 1000 nmoles/tube increased the 3-methoxytyramine recovered above controls by 0.0, 6.88, 44.55, 129.47 and 5.8, 13.9, 50.58, 121.31 nmoles for SAM and MPP+, respectively. The dopamine that remained unreacted was dose-dependently decreased. MPTP had no significant effect. The ability of MPP+ to serve as a methyl donor may represent a mechanism for the toxicity of MPP+.
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PMID:1-Methyl-4-phenylpyridinium (MPP+) but not 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) serves as methyl donor for dopamine: a possible mechanism of action. 159 Sep 12

The role of opioid receptors in long-term potentiation (LTP) of the medial (MPP) and lateral (LPP) divisions of the perforant path-granule cell projection was investigated in urethane anesthetized rats. A stimulating electrode was positioned in the dorsomedial or ventrolateral aspect of the angular bundle for selective activation of the MPP and LPP, respectively. A push-pull cannula served to focally perfuse artificial cerebrospinal fluid (ACSF) across the perforant path terminal zone, while perforant path evoked potentials were monitored in the dentate hilus. Robust LTP of the excitatory postsynaptic potential (EPSP) initial slope and population spike height was induced by high frequency stimulation (400 Hz, 8 bursts of 8 pulses) applied to the medial or lateral perforant path in rats perfused with standard medium. In the lateral perforant path, a putative proenkephalin system, LTP of the EPSP and population spike was blocked when ACSF containing 100 microM of the opioid receptor antagonist naloxone was present during the tetanus, while perfusion with 0.1 microM naloxone prevented EPSP potentiation but only reduced the magnitude of the population spike increase. Naloxone had no effect on LTP induction in the MPP. Importantly, 0.1 microM ICI 174,864, a selective antagonist of delta opioid receptors, blocked LTP of synaptic transmission in the LPP while leaving the population spike increase intact. The results indicate that LTP of synaptic transmission in the LPP requires activation of delta opioid receptors, while 'non-delta' opioid receptors may be involved in augmenting granule cell output. This opioid receptor-dependent LTP illustrates peptidergic regulation of synaptic plasticity in the hippocampus.
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PMID:Delta opioid receptor activation is required to induce LTP of synaptic transmission in the lateral perforant path in vivo. 166 45

Many precursors of mitochondrial proteins are processed in two successive steps by independent matrix peptidases (MPP and MIP), whereas others are cleaved in a single step by MPP alone. To explain this dichotomy, we have constructed deletions of all or part of the octapeptide characteristic of a twice cleaved precursor (human ornithine transcarbamylase [pOTC]), have exchanged leader peptide sequences between once-cleaved (human methylmalonyl-CoA mutase [pMUT]; yeast F1ATPase beta-subunit [pF1 beta]) and twice-cleaved (pOTC; rat malate dehydrogenase (pMDH); Neurospora ubiquinol-cytochrome c reductase iron-sulfur subunit [pFe/S]) precursors, and have incubated these proteins with purified MPP and MIP. When the octapeptide of pOTC was deleted, or when the entire leader peptide of a once-cleaved precursor (pMUT or pF1 beta) was joined to the mature amino terminus of a twice-cleaved precursor (pOTC or pFe/S), no cleavage was produced by either protease. Cleavage of these constructs by MPP was restored by re-inserting as few as two amino-terminal residues of the octapeptide or of the mature amino terminus of a once-cleaved precursor. We conclude that the mature amino terminus of a twice-cleaved precursor is structurally incompatible with cleavage by MPP; such proteins have evolved octapeptides cleaved by MIP to overcome this incompatibility.
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PMID:Cleavage of precursors by the mitochondrial processing peptidase requires a compatible mature protein or an intermediate octapeptide. 167 32


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