bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopaminergic Neurotoxicity In Vivo and Inhibition of Mitochondrial Respiration In Vitro by Possible Endogenous Pyridinium‐Like Substances
Authors: Sayre Lawrence M. , Wang Fengjiang , Arora Pramod K. , Riachi Naji J. , Harik Sami I. , Hoppel Charles L. 
Published: October 2006

AbstractElucidation of the mechanism(s) by which 1‐methyI‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and its active metabolite l‐methyl‐4‐phenylpyridinium (MPP+) cause parkinsonism in humans and other primates has prompted consideration of possible endogenous MPTP/MPP+‐like ncurotoxins in the etiology of idiopathic Parkinson's disease. Here we examined inhibition of mitochondrial respiration in vitro and neurotoxicity in rats in vivo produced by β‐carbolinium compounds that are presumed to form following Pictet‐Spengler cyclization of serotonin. We also evaluated N‐methyiisoquinolinium, a putative endogenous neurotoxin, in the same manner. The latter compound exhibited MPP+ like mitochondrial respiratory inhibition, whereas the β‐carbotinitim compounds, although more potent inhibitors of electron transport, exhibited weak accumulation‐ dependent enhancement of inhibition in intact mitochondria. It is interesting that the β‐carbolinium compounds inhibited succinate‐as well as glutamate‐supported respiration, and are best described as inhibitor‐uncouplers. The results of partitioning experiments suggest that both the low accumulation potential and the inhibition of succinate respiration may be a consequence of the β‐carboliniums being in equilibrium with neutral “anhydro” bases. Relative to MPP+, all compounds tested had weak dopaminergic uptake activity in vitro and weak dopaminergic toxicity in vivo, consistent with other findings of relatively low neurotoxic potential for presumed endogenous pyridiniums.
The Death Programme in Cultured Sympathetic Neurones Can Be Suppressed at the Posttranslational Level by Nerve Growth Factor, Cyclic AMP, and Depolarization
Authors: Edwards Susan N. , Buckmaster Anne E. , Tolkovsky Aviva M. 
Published: October 2006

AbstractWe have examined whether sympathetic neurones that have lost the potential to be rescued by protein and RNA synthesis inhibitors after a period of nerve growth factor (NGF) deprivation are irreversibly committed to die. We found that 15 h after withdrawal of NGF from 7‐day cultures of neonatal rat superior cervical ganglion neurones, 50% of the neurones lost the potential to be rescued by cycloheximide but that NGF rescued most of the neurones. By 22 h after NGF withdrawal, only 10% of the neurones were rescued by inhibition of macromolecular synthesis with cycloheximide, puromycin, or actinomycin D, but as many as 60‐80% of the neurones were rescued by NGF. This is after the time at which a DNA “ladder,” consistent with cell death by apoptosis, was first detected (18 h). As long as 27 h of NGF withdrawal was required before 50% of the neurones lost the potential to be rescued by NGF. The survival‐promoting agent 8‐(4‐chlorophenylthio)cyclic AMP (CPTcAMP) or depolarization with 50 mM K.C1 (HK) rescued neurones with kinetics similar to those of NGF, and rescue by all three agents did not require protein synthesis. Thus, NGF, CPTcAMP, and HK can rescue neurones deprived of NGF at much later times than either protein or RNA synthesis inhibitors by acting at the posttranslational level, a finding suggesting that initiation of the cell death programme in sympathetic neurones is not an irreversible step.
Evidence for Nonrandom Distribution of GD1 a Ganglioside in Rabbit Brain Microsomal Membranes
Authors: Palestini P. , Masserini M. , Fiorilli A. , Calappi E. , Tettamanti G. 
Published: October 2006

AbstractGD1a is the major ganglioside of rabbit brain microsomal membranes and occurs mainly with two molecular species, containing the C18:1 (62.3%) and C20:1 (37.7%) long‐ chain bases. The membranes were exposed to Vibrio cholerae (VC) sialidase under conditions where the enzyme hydrolyzed only GD1a(∼9%), producing GM1 ganglioside, whereas the other gangliosides remained virtually unaffected. The long‐ chain‐base analysis showed that newly‐formed GM1 contained ∼68% of the C20:1 molecular species. This indicates that VC sialidase did not randomly affect the two molecular species of GD1a but hydrolyzed preferentially the C20:1 one. In similar experiments, GD1a was inserted into the external layer of phosphatidylcholine vesicles and incubated with VC sialidase under conditions producing ∼ 10% hydrolysis. Long‐ chain‐base analysis showed that the proportion of C20:1 species in GM1 was 25.1% using vesicles composed of dipal‐mitoylphosphatidylcholine and 42.3% with egg phosphatidylcholine, whereas it was 39.2% in the starting GD1a. Therefore, in artificial membranes, VC sialidase acted preferentially on the C18:1 or C20:1 molecular species, depending on the length and unsaturation of the phospholipid fatty acids. Because VC sialidase is known to affect molecular dispersions more easily than packed aggregations of the gangliosidic substrate, the data suggest that in rabbit brain microsomal membranes the GD1a ganglioside molecular species carrying C20:1 long‐chain base are more molecularly dispersed than those containing C18:1 long‐chain base.
Differential Turnover Rates of D1 Dopamine Receptors in the Retina and in Distinct Areas of the Rat Brain
Authors: Giorgi O. , Pibiri M. G. , Biggio G. 
Published: October 2006

AbstractThe present study was designed to examine the steady‐state density and the turnover rates of D1 dopamine (DA) receptors in the striatum, nucleus accumbens, substantia nigra, and retina of the rat. The turnover rates were measured by monitoring the repopulation kinetics of D1 DA receptors labelled with [3H]SCH 23390 after the irreversible inactivation induced by a single dose of N‐ethoxycarbonyl‐2‐ethoxy‐ 1, 2‐dihydroquinoline (10 mg/kg s.c.). The repopulation of D1 DA receptors could be described adequately in all the neural tissues investigated by a theoretical model that assumes a constant rate of receptor production (i.e., zero order) and a rate of degradation that is dependent on the receptor density at any time (i.e., first order). The quantitative analysis of the experimental data using this theoretical model revealed significant regional differences in the rates of receptor production and degradation. Thus, the receptor production rates determined in the nucleus accumbens and striatum (8.03 and 9.96 fmol/mg of protein/h, respectively) were four‐ to sixfold larger than those measured in the substantia nigra (1.80 fmol/mg of protein/h) and retina (1.50 fmol/mg of protein/h). On the other hand, the receptor degradation rates in the striatum, nucleus accumbens, and retina (0.0093 h−1, 0.0110 h−1, and 0.0123 h−1, respectively) were 2.6–3.5‐fold larger than the receptor degradation rate in the substantia nigra (0.0035 h−1).
Phosphatidic Acid Accumulation and Catecholamine Release in Adrenal Chromaffin Cells: Stimulation by High Potassium and by Nicotine, and Effect of a Diacylglycerol Kinase Inhibitor R 59 022
Authors: Owen P. Jane , Jones J. Alison , Boarder Michael R. 
Published: October 2006

AbstractUsing primary cultures of bovine adrenal chromaffin cells labelled with 32Pi, we show that stimulation with bradykinin, nicotine, or a depolarising concentration of potassium stimulates the accumulation of [32P]phosphatidic acid. The effects of nicotine and potassium are smaller than the effect of bradykinin, and are dependent entirely on extracellular calcium. The diacylglycerol kinase inhibitor R 59 022 attenuates the formation of phosphatidic acid by nicotine and depolarising concentrations of potassium. This inhibitor also blocks the nicotine and potassium stimulation of nor‐ adrenaline release from Chromaffin cells. Using 45Ca2+ influx studies, we show that the nicotine‐evoked calcium influx is also attenuated by R 59 022. These observations contrast with those in another report in which we showed that bradykinin stimulation of either [32P]phosphatidic acid accumulation or noradrenaline release is not affected by R 59 022. It is likely that the calcium influx produced by nicotine and depolarising potassium is blocked by R 59 022 by a mechanism that is independent of its ability to block diacylglycerol kinase. The nicotine‐ and potassium‐stimulated [32P]phosphatidic acid accumulation is a consequence of this calcium influx and presumably reflects calcium activation of either phospholipase C or phospholipase D.
The Mouse Dopamine D2A Receptor Gene: Sequence Homology with the Rat and Human Genes and Expression of Alternative Transcripts
Authors: Mack Kenneth J. , Todd Richard D. , O'Malley Karen L. 
Published: October 2006

AbstractTo understand the possible involvement of dopamine receptors in the pathogenesis of various neurological disorders, we have cloned and sequenced a dopamine D2A receptor gene from the mouse. A mouse genomic library was screened with probes derived from the published sequence of a rat D2A receptor cDNA. Using restriction endonuclease mapping, Southern blotting, and DNA sequencing, we have determined the cDNA sequence and genomic organization of the mouse D2A receptor gene. Unlike other guanine nucleotide‐binding protein‐coupled receptors, but similar to its rat and human counterparts, the mouse D2A receptor gene has seven introns and spans at least 30 kb of genomic DNA. The mouse D2A sequence shows 99% amino acid homology with the rat and 95% amino acid homology with the human sequence. As would be predicted, sequence differences are significantly more frequent outside of the hypothesized transmembrane spanning domain regions of the protein. Using the polymerase chain reaction with primers made from neighboring exons, we have identified two alternatively spliced D2A transcripts in the mouse. However, in contrast to the other species studied, the mouse expresses primarily the mRNA representing the larger, 444‐amino‐acid form of the receptor. Mouse pituitary expresses only the mRNA of the 444‐amino‐acid form of the D2A receptor. Hence, the mouse may offer the best model to study the in vivo physiology of the long form of the D2A receptor.
Mechanism of Neurotransmitter Release Elicited by the Preferential α1‐Adrenergic Receptor Agonist Phenylephrine in Superfused Superior Cervical Ganglion Cells in Culture
Authors: Schwartz Dean D. , Malik K. U. 
Published: October 2006

AbstractPhenylephrine increased [3H]norepinephrine efflux and accumulation of cyclic AMP in cultured rat superior cervical ganglion cells supervised with Tyrode's solution. The purpose of this study was to determine the mechanism and relationship between these two events. Electrical stimulation (1–2 Hz), potassium chloride (50 mM), and the preferential α1‐adreneargic receptor agonist phenylephrine (1–100 μM) increased fractional tritium efflux, whereas methoxamine, cirazoline, and amidephrine were relatively ineffective. Phenylephrine, but not methoxamine and cirazoline, also iacreased cyclk AMP accumulation. Phenylephrine‐induced tritium efflux was not altered by α‐and β‐adrenergic receptor antagonists or by removal of extracellular calcium. Phenylephrine‐induced cyclic AMP accumulation was blocked by the β‐adrenergic receptor antagonists propranolol and atenokd. Focskolin (10 μM) and the nonhydrolyzable cyclic AMP analogue 8‐(4‐chlorophenylthio)cyclic AMP (100 μM) had minimal effect on tritium efflux. However, phenylephrine‐evoked increase in tritium efflux was dose dependency attenuated by the neuronal uptake blocker cocaine, and phenylephrine dose‐dependently inhibited the incorporation of [3H]norepinephrine into neuronal stores. We conclude that the increase in tritium efflux induced by Phenylephrine is independent of cyclic AMP accumulation and appears to be mediated by uptake of phenylephrine via the neuronal carrier‐mediated amine transport process, which in tarn promotes efflux of the adrenergic transmitter from its storage sites.
Comparative Incorporation of Proenkephalin‐Derived Peptides, Chromogranin A, and Dopamine β‐Hydroxylase into Chromaffin Vesicles
Authors: Wilson Steven P. , Corcoran James J. , Kirshner Norman 
Published: October 2006

AbstractThe incorporation of enkephalin‐containing peptides (ECPs) derived from proenkephalin into chromaffin vesicles was examined in primary cultures of adrenal medullary chromaffin cells. Cells were pulse‐labeled with [35S]methionine and chased for periods up to 24 h. Chromaffin vesicles in cell homogenates were then fractionated by density gradient centrifugation and the presence of [35S]Met‐enkephalin sequences in gradient fractions determined. 35S‐ECPs were incorporated into particles suggestive of immature vesicles within 1–2 h after radiolabeling. Vesicle maturation, measured by co‐equilibration of 35S‐ECPs and total ECPs in the gradients, was complete within 9–12 h and was unaffected by treatments that increase proenkephalin synthesis. Incorporation of [35S]chromogranin A into chromaffin vesicles followed a similar time course, but 35S‐labeled dopamine β‐hydroxylase was much more slowly incorporated, possibly reflecting differences in incorporation of membrane and soluble components. In summary, the data demonstrate that ECPs are rapidly sequestered in immature chromaffin vesicles, a process unaltered by changing rates of proenkephalin synthesis.
Brain Micro vessel 12‐Hydroxyeicosatetraenoic Acid Is the (S) Enantiomer and Is Lipoxygenase Derived
Authors: Moore Steven A. , Giordano Michael J. , Kim Hee‐Yong , Salem Norman , Spector Arthur A. 
Published: October 2006

Abstract12‐Hydroxyeicosatetraenoic acid (12‐HETE) production from arachidonic acid by cerebral microvessels isolated from perfused adult murine brain was reduced by the lipoxygenase inhibitors baicalein, esculetin, gossypol, nordihydroguaiaretic acid, and quercetin. Except for quercetin and gossypol, the IC50 did not exceed 10 μM. Each inhibitor, except baicalein, also decreased microvessel prostaglandin production when present in concentrations above their IC50 value for 12‐HETE. In contrast, inhibitors of the cytochrome P450 monooxygenase system, clotrimazole. metyrapone, and proadifen (SKF‐525A), had little effect on microvessel 12‐HETE production. Chiral phase HPLC analysis revealed that only the (5) enantiomer of 12‐HETE was formed. The major microvessel metabolite of eicosapentaenoic acid co‐eluted with 12‐hydroxyeicosapentaenoic acid (12‐HEPE) on reverse‐phase HPLC and the (S) enantiomer of 12‐HEPE on chiral phase HPLC. Furthermore, like 12‐HETE. 12‐HEPE production was blocked by lipoxygenase inhibitors. These studies demonstrate that brain microvessels produce only the (5) enantiomeric 12‐hydroxy derivatives of both arachidonic acid and eicosapentaenoic acid by the action of a lipoxygenase that can be selectively inhibited by baicalein. Since arachidonic acid and eicosapentaenoic acid are available to cerebral blood vessels in certain pathological settings, these 12‐hydroxy acid lipoxygenase products may mediate some of the cere‐brovascular dysfunction that occurs following stroke, brain trauma, or seizures.
Saturable Transport of Manganese(II) Across the Rat Blood‐Brain Barrier
Authors: Murphy Vincent A. , Wadhwani Kishena C. , Smith Quentin R. , Rapoport Stanley I. 
Published: October 2006

AbstractUnanesthetized adult male rats were infused intravenously with solutions containing 54Mn (II) and one of six concentrations of stable Mn(II). The infusion was timed to produce a near constant [Mn] in plasma for up to 20 min. Plasma was collected serially and on termination of the experiment, samples of CSF, eight brain regions, and choroid plexus (CP) were obtained. Influx of Mn (JMn) was calculated from uptake of 54Mn into tissues and CSF at two different times. Plasma [Mn] was varied 1,000‐fold (0.076–78 nmol/ml). Over this plasma concentration range, JMn increased 123 times into CP, 18–120 times into brain, and 706 times into CSF. CP and brain JMn values fit saturation kinetics with Km (nmol/ml) equal to 15 for CP and 0.7–2.1 for brain, and Vmix (10–2 nmol · g−1· s−1) of 27 for CP and 0.025–0.054 for brain. Brain JMn except at cerebral cortex had a nonsaturable component. CSF JMn varied linearly with plasma [Mn]. These findings suggest that Mn transport into brain and CP is saturable, but transport into CSF is nonsaturable.
Adenosine Inhibits Histamine‐Induced Phosphoinositide Hydrolysis Mediated via Pertussis Toxin‐Sensitive G Protein in Human Astrocytoma Cells
Authors: Nakahata Norimichi , Abe Marilene T. , Matsuoka Isao , Ono Tomoyuki , Nakanishi Hironori 
Published: October 2006

AbstractThe effect of adenosine on phosphoinositide hydrolysis was examined in 1321N1 human astrocytoma cells. Adenosine, L‐N6‐phenylisopropyladenosine (l‐PIA), and 5‐ (N‐ethylcarboxamido)adenosine (NECA) inhibited histaminc‐stimulated accumulation of inositol phosphates in a concentration‐dependent manner. The potency order of adenosine analogues for inhibition of inositol phosphate accumulation was l‐PIA > adenosine > NECA, a finding indicating that A1‐class adenosine receptors are involved in the inhibition. The reduction in inositol phosphate accumulation by l‐PIA was blocked by an adenosine receptor antagonist, 8‐phenyltheophylline. Stimulation of A1‐class adenosine receptors inhibited isoproterenol‐stimulated cyclic AMP accumulation as well as histamine‐induced inositol phosphate accumulation. Both inhibitory effects were blocked by pretreatment of the cells with pertussis toxin [islet‐activating protein (IAP)]. l‐PIA also inhibited guanosine 5′‐(γ‐thio)triphosphate (GTPγ)‐stimulated accumulation of inositol phosphates in membrane preparations, and 8‐phenyltheophylline antagonized the inhibition. l‐PIA could not inhibit GTPγS‐induced accumulation of inositol phosphates in IAP‐treated membranes. Gi/G0, purified from rabbit brain, inhibited GTPγS‐stimulated accumulation of inositol phosphates in a concentration‐dependent manner in membrane preparations. These results suggest that stimulation of Ar class adenosine receptors interacts with the IAP‐sensitive G protein(s), resulting in the inhibitions of phospholipase C as well as adenylate cyclase in human astrocytoma cells.
Characterization of Delta‐Sleep‐Inducing Peptide‐Evoked Release of Met‐Enkephalin from Brain Synaptosomes in Rats
Authors: Nakamura Akihiro , Sakai Kenji , Takahashi Yukie , Shiomi Hirohito 
Published: October 2006

AbstractDelta‐sleep‐inducing peptide (DSIP) stimulates the release of Met‐enkephalin (Met‐ENK) from superfused slices of the rodent lower brainstem in vitro. In our present study, DSIP (10–10–10–9M) induced a significant release of Met‐ENK from medullary synaptosomes of rats. This DSIP‐evoked release of Met‐ENK was Ca2+ dependent and tetro‐dotoxin (TTX) insensitive. Furthermore, DSIP (10–11–10–9M) significantly increased 45Ca2+ uptake in medullary synaptosomes. These results demonstrate that DSIP acts directly on the nerve endings of Met‐ENK‐containing neurons to release this pentapeptide by generating a Ca2+ influx into these neurons. Effects of DSIP on Met‐ENK release in other discrete brain regions were also studied. Significant DSIP‐evoked Met‐ENK release from synaptosomes was observed in the cortex, hypothalamus, and midbrain (at concentrations of 10–10 and 10–9M) and in the hippocampus and thalamus (only at 10–9M), but not in the striatum. In the hypothalamus, the release of Leu‐enkephalin from its synaptosomes was slightly, but not significantly, enhanced by DSIP (10–10–10–8M). Our findings demonstrate that DSIP triggered a Ca2+ influx in nerve endings to induce a subsequent release of Met‐ENK from neurons in only certain brain regions.
Splicing Pattern of Gsα mRNA in Human and Rat Brain
Authors: Granneman James G. , Bannon Michael J. 
Published: October 2006

AbstractGsα, the GTP‐binding protein that mediates receptor stimulation of adenylyl cyclase, exists in small (Gsα‐s) and large (Gsα‐L) molecular forms. Previous work has established that these Gsα isoforms are products of alternatively spliced Gsα pre‐mRNA. The present work examined the splicing pattern of Gsα mRNA in rat and human brain using a method based upon the polymerase chain reaction. In rat brain, transcripts encoding Gsα‐L were most abundant and constituted 92% of total Gsα mRNA in hippocampus and cerebral cortex and 84% in striatum. Compared to rat brain, the relative abundance of Gsα‐L mRNA was less in human brain and constituted 84% of total Gsα mRNA in hippocampus and cortex and 66% in striatum. In addition, it was found that approximately 40% of the Gsα‐S mRNA utilizes an alternative splice site that encodes serine at amino acid 72. No regional variations in this splicing pattern were found.
High Expression of the HNK‐1/L2 Carbohydrate Epitope in the Major Glycoproteins of Shark Myelin
Authors: Zand Dina , Hammer Jeffrey , Gould Robert , Quarles Richard 
Published: October 2006

AbstractThe major 24‐ and 28‐kDa glycoproteins in shark PNS and CNS myelin express high levels of the adhesion‐associated HNK‐1/L2 carbohydrate epitope. The 28‐kDa protein, but not the 24‐kDa protein, cross‐reacts strongly with one of two anti‐bovine PO antisera not previously tested against fish myelin proteins. Shark PNS and CNS myelin also contains smaller amounts of high‐molecular‐weight HNK‐1‐positive proteins, including a prominent broad band in the 65–85‐kDa range. Although myelin‐associated glycoprotein (MAG) is well known to react with HNK‐1 in some mammals, monoclonal and polyclonal anti‐MAG antibodies did not react with the high‐molecular‐weight HNK‐1‐positive material in shark myelin, a result suggesting that it is not a MAG‐like protein. The high expression of the HNK‐1/L2 epitope in glycoproteins of shark myelin, including the major Po‐related ones, suggests that this adhesion‐related carbohydrate structure may have had an important role in the molecular evolution of the myelinating process.
Role of Dendritic Dopamine of the Substantia Nigra in the Modulation of Nigrocollicular γ‐Aminobutyric Acid Release: In Vivo Studies in the Rat
Authors: Le Boulch N. Lantin , Truong‐Ngoc N. A. , Gauchy C. 
Published: October 2006

AbstractThe release of γ‐[3H]aminobutyric acid ([3H]GABA) newly synthesized from [3H]glutamine was estimated in the superior colliculus of ketamine‐anesthetized rats superfused via a push‐pull cannula. A significant amount of [3H]GABA was spontaneously released in the superior colliculus (582 ± 49 pCi/10 min). A major part of the large K+‐evoked increase of the [3H]GABA release was Ca2+ dependent. When neuronal activity of the substantia nigra was enhanced by nigral application of K+ (30 mM) or bicuculline (10–4M), a persistent increase of the collicular [3H]GABA release was observed (60 and 80%, respectively). Conversely, when nigral activity was reduced by nigral application of GABA (10–4M) or superfusion with a Ca2+ free medium, a sustained decrease of the collicular [3H]GABA release was observed (‐30 and ‐40%. respectively). Following the nigral application of a selective D2‐receptor agonist, RU 24926 (10–5M), for 30 min in 6‐hydroxydopamine‐lesioned rats, a phasic increase (60%) of the collicular [3H]GABA release was detected. This effect could result from an activation of nigrocollicular GABAergic neurons by D2‐receptor stimulation, because nigral activity and collicular release of [3H]GABA changed in a parallel direction.