bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Alterations of Opiate Receptor Subtypes in Mono sodium Glutamate‐Treated Rats
Authors: Young Elizabeth , Olney John , Akil Huda 
Published: October 2006

Abstract:Neonatal treatment of rats with monosodium glutamate (MSG) has been demonstrated to destroy cell bodies of neurons in the arcuate nucleus including the brain beta‐endorphin (B‐END) system. The effects on opiate receptors of the loss of B‐END is unknown. Neonatal rats were treated with MSG as previously described. After reaching maturity (7‐9 months), MSG‐treated rats and litter‐matched untreated control rats were decapitated and brains dissected into brain regions. Opiate receptor assays were run with [3H]morphine (mu receptor ligand) and [3H]D‐alanine2‐D‐leucine5 (DADL) enkephalin (delta receptor ligand) for each brain region for both MSG and control rats simultaneously. Scatchard plot analyses showed a selective increase in delta receptors in the thala‐mus only. No corresponding change in mu receptors in the thalamus was found. The cross‐competition IC50 data supported this conclusion, showing a loss in the potency of morphine in displacing [3H]DADL enkephalin in the thalamus of MSG‐treated rats. This shift in delta receptors produced an IC50 displacement pattern in thalamus, ordinarily a mu‐rich area, similar to that of striatum or cortex, delta‐rich areas, again indicating an increase in delta receptors. Similar changes in delta receptors in other brain regions were not found. These results represent one of the few examples of a selective and localized shift in delta with no change in mu sites. Furthermore, the delta increase may reflect an up‐regulation of the receptors in thalamus after chronic loss of the endogenous opioid B‐END.
Norepinephrine Depletion in the Spinal Cord Gray Matter of Rats with Experimental Allergic Encephalomyelitis
Authors: White S. R. , Bhatnagar R. K. , Bardo M. T. 
Published: October 2006

Abstract:Norepinephrine and dopamine concentrations were determined by radioenzymatic assay in discrete gray matter regions of the spinal cords of rats with experimental allergic encephalomyelitis (EAE). Norepinephrine was depleted in most spinal cord regions of EAE rats compared with controls, whereas dopamine depletion in EAE rats was restricted to the cervical dorsal horn. There was a rostrocaudal gradient of norepinephrine reduction in the spinal cords of the EAE rats with most severe depletion in the lumbar region. The results of this experiment confirmed recent anatomical observations that suggested that catecholamine‐fluorescent axons and terminals were damaged in spinal cords of rats with EAE.
Cholinergic‐Adrenergic Receptor Interactions in Cerebral Microvessels
Authors: Grammas P. , Diglio C. A. , Giacomelli F. , Wiener J. 
Published: October 2006

Abstract:Enriched capillary preparations isolated from rat cerebral cortex were used to evaluate cholinergic‐adrenergic receptor interactions in cerebral endothelium. Possible receptor interactions were determined by measuring an intracellular mediator, cyclic AMP and alterations in GTP‐sensitive agonist binding. Unstimulated microvessel homogenates generate 66 ± 16 pmol/mg/10 min of cyclic AMP. Adrenergic agonists norepinephrine and isoproterenol increase cyclic AMP to 147 ± 31 and 149 ± 23 pmol/mg/10 min, respectively. Addition of the muscarinic agonist carbachol has no effect on basal cyclic AMP but it completely blocks the stimulation elicited by adrenergic agonists. The displacement of quinuclidinyl benzilate (QNB) by carbachol yields an IC50 of 1.5 ± 0.45 x 10−4M and a Hill coefficient of 0.54 ± 0.07, indicating a heterogeneous population of binding sites. Guanine nucleotides shift the displacement curve to the right (IC50, 4.7 ± 0.16 x 10−4M) and convert the binding site population to greater homogeneity (0.76 ± 0.18). Isoproterenol prevents both the affinity shift and binding site conversion evoked by guanine nucleotides. These data suggest that cholinergic‐adrenergic interactions occur at both the level of receptor binding and the generation of an intracellular messenger. Since cyclic AMP has been purported to play a role in regulation of blood–brain barrier permeability, the existence of adrenergic‐cholinergic, i.e., excitatory‐inhibitory modulators of adenylate cyclase in cerebral endothelium, suggests that these receptors may mediate physiological and/or pathological alterations of cerebrovascular permeability.
Distribution of Guanine Deaminase in Mouse Brain
Authors: Berger Sosamma J. , Carter Joyce G. , Lowry Oliver H. 
Published: October 2006

Abstract:Guanine deaminase was measured in nearly 100 different areas of mouse brain. The levels are relatively high in all parts of the telencephalon, both gray and white. It is especially active in parts of the olfactory tubercle and amygdala. Levels in the diencephalon range from low to as high as in the telencephalon. Brain areas caudal to the diencephalon, including all parts of the cerebellum, are almost uniformly below the level of detection. The enzyme is also virtually absent from the retina. The extreme range of concentration suggests that guanine deaminase might play a role in the metabolism of a neuroeffector.
Studies on a Cerebellar 50,000‐Dalton Protein Associated with Cerebellar Hypoplasia in Jaundiced Gunn Rats: Its Identity with Glial Fibrillary Acidic Protein as Evidenced by the Improved Immunoblotting Method
Authors: Aono Sachiko , Sato Hiroshi , Semba Reiji , Kashiwamata Shigeo , Eng Lawrence F. 
Published: October 2006

Abstract:On the basis of our previous findings that a 50,000‐dalton protein (GR‐50) shows a marked increase in the hypoplastic cerebellum of jaundiced homozygous Gunn rats and its electrophoretic behavior is similar to that of glial fibrillary acidic protein (GFAP), we tried to identify GR‐50 as GFAP by two‐dimensional electropho‐resis of rat cerebellar membrane proteins using an improved immunoblotting method. In this method a blot immunostained for a specific antigen was also visualized for other proteins, thereby enabling us to determine the location of the antigen on the blot more precisely. With the methodology it was found that GFAP antigen occupied exactly the same position as GR‐50 on the blot, suggesting strongly the identity of both proteins. Immunohistochemical studies revealed that in the cerebellum of homozygotes compared with that of heterozygotes GFAP antigen was greatly increased and that it was especially rich in the homozygous rat cerebellar lobules with a high degree of hypoplasia. Further, it was shown that not only the fibers of the Bergmann glial cells but also their somata were intensely immunostained in the affected lobules. A 47,000‐dalton protein (SG‐47), which has been reported to be increased in staggerer mutant mice with cerebellar hypoplasia, also immunoreacted with the antiserum to GFAP.
Complete Conversion of Brain D2 Dopamine Receptors from the High‐ to the Low‐Affinity State for Dopamine Agonists, Using Sodium Ions and Guanine Nucleotide
Authors: Grigoriadis Dimitri , Seeman Philip 
Published: October 2006

Abstract:Since previous work had shown that brain D2 3,4‐dihydroxyphenylethylamine (dopamine) receptors were only partly converted from their high‐affinity state to their low‐affinity state, we here tested whether it was possible to obtain a complete 100% conversion of these receptors into their low‐affinity state. It was first essential to resolve the components of [3H]spiperone binding to dopaminergic sites and nondopaminergic sites in rat striatal homogenates. In the presence of 50 μMS‐sulpiride (to occlude the dopaminergic sites), therefore, we first determined that the residual binding of [3H]spiperone (approximately 20%) was inhibited by serotonergic agonists much more effectively than dopamine or noradrenaline, thus identifying the serotonergic component of [3H]spiperone binding. Thus, dopamine (or ADTN) inhibited the binding of [3H]spiperone at a high‐affinity site (with dissociation constant of 10 nM dopamine), at a low‐affinity site (with dissociation constant of 2,000 nM dopamine), and at the serotonergic site (with dissociation constant of 50,000 nM dopamine). In the absence of sodium ions, the high‐affinity site was about 50% occupied by [3H]spiperone, and guanine nucleotide had no effect on this proportion. In the presence of 120 mM NaCl, however, the high‐affinity site was reduced to 15% and guanine nucleotide completely eliminated this high‐affinity site, 100% of the sites having been completely converted to their low‐affinity state. Using [3H]N‐propyl‐norapomorphine to label the high‐affinity state of the dopamine receptor, 50% conversion into the low‐affinity state occurred at 45 mM NaCl, 69 mM NaCl, and 202 mM KCl. We conclude that it is possible to convert brain D2 dopamine receptors completely into their low‐affinity state, in the presence of NaCl and a guanine nucleotide, providing that appropriate allowance is made for the serotonergic component of [3H]spiperone binding.
Possible Allosteric Interaction of 4‐Aminopyridine with Rat Brain Muscarinic Acetylcholine Receptors
Authors: Lai Wi S. , Ramkumar Vickram , El‐Fakahany Esam E. 
Published: October 2006

Abstract:The interaction of the potassium channel blocker 4‐aminopyridine (4‐AP) and its analogs with muscarinic acetylcholine receptors was studied in rat brain homogenate. 4‐AP displaced specific [3H]quinuclidinyl benzilate ([3H]QNB) binding in a concentration‐dependent fashion. Hill coefficient values decreased with increasing the concentration of [3H]QNB and different analogs of 4‐AP demonstrated varying potencies. Scatchard analysis of saturation isotherms of specific [3H]QNB binding showed that low concentrations of 4‐AP slightly reduced maximum binding without affecting the equilibrium dissociation constant, whereas higher concentrations reduced maximum binding further and significantly increased the equilibrium dissociation constant. Schild plots of these data resulted in curvilinear functions. The results are discussed in terms of possible allosteric interactions between potassium channels and muscarinic receptor binding sites.
Characterization of K Opioid Receptors in Neurosecretosomes from Bovine Posterior Pituitary
Authors: Pesce Guido , Lang Michael A. , Russell James T. , Rodbard David , Gainer Harold 
Published: October 2006

AbstractThe binding properties of opioid receptors on isolated nerve terminals (neurosecretosomes) from bovine posterior pituitaries were characterized. Both [3H]etorphine and [3H]ethylketocyclazocine ([3H]EKC) showed high‐affinity binding with complex binding isotherms, consistent with the presence of multiple classes of binding sites. [D‐Ala2,D‐Leu5]enkephalin showed no specific binding and failed to displace [3H]etorphine at high concentrations, indicating the absence of μ, δ, or benzomorphan (K2) sites. Mathematical modelling of the data suggested the presence of three classes of binding sites. The first was of high affinity with Kd values of 0.9 and 2.0 nM for etorphine and EKC, respectively. The second class of sites appeared to bindetorphine with a KD of 150 nM, and EKC with extremely low affinity (unmeasurable binding). The third class of sites was characterized by KD values of 7 and 2 μM for etorphine and EKC, respectively. These results indicate that the nerve terminals of bovine posterior pituitary contain opioid binding sites of the K type. Futhermore, these binding sites appear heterogeneous, consisting of at least two and possibly more subtypes or states.
Age‐Associated Changes in Pineal Adrenergic Receptors and Melatonin Synthesizing Enzymes in the Wistar Rat
Authors: Dax Elizabeth M. , Sugden David 
Published: October 2006

AbstractThe nocturnal stimulation of pineal melatonin synthesis and elevation of serum melatonin is known to be reduced in old age in several species. In Wistar rats the capacity of the β‐adrenoceptor to develop supersensitivity (increase in Bmax) during the light period of the diurnal light/dark cycle is lost during maturation (3–6 months) rather than old age. Further, the present study shows that neither the α1‐ nor β‐adrenoceptor density of the pineal declines as rats age. Pineal hydroxyindole‐O‐methyltransferase activity does fall (17–55%) in rats after 18 months of age, but nocturnal pineal arylalkylamine N‐acetyltransferase activity is not significantly altered. Thus, from examination of these parameters across the life span of the rat, it seems likely that the reported reduction in serum melatonin in old animals is related to a reduced capacity of the pineal to synthesize melatonin, rather than an altered responsiveness of the gland to neural stimulation.
Developmental Pattern for Deoxyhypusine Hydroxylase in Rat Brain
Authors: Abbruzzese Alberto 
Published: October 2006

AbstractDeoxyhypusine hydroxylase catalyzes the formation of hypusine from deoxyhypusine in a precursor form of eukaryotic initiation factor 4D (eIF‐4D). The enzymatic activity was examined in mammalian brain homogenates and the results were consistent with the existence of deoxyhypusine hydroxylase levels comparable to those occurring in other mammalian tissues. Interspecies differences in the enzyme distribution were quite limited, with the highest specific activity values observed in cow brain (1.82 units/ mg of protein). In the rat the enzyme was found to be unevenly distributed among various brain regions. The parietal cortex contained the highest specific activity (2.1 units/mg of protein). Rat brain deoxyhypusine hydroxylase was mainly present in the postmicrosomal supernatant (81% of the total activity). The highest specific activity (3 units/mg of protein) was observed in the rat brain during the first few days of life. Thereafter the activity started to decline, and continued to do so for 15 days, remaining throughout the rest of life at levels of less than one‐half that of newborn.
Choline Transport and Metabolism in Soman‐or Sarin‐Intoxicated Brain
Authors: Drewes Lester R. , Singh Ashok K. 
Published: October 2006

AbstractThe metabolism and blood‐brain transport of choline (Ch) were investigated in perfused canine brain under control conditions and for 60 min after inhibition of brain cholinesterases by the organophosphorus (OP) compounds soman (pinacolylmethylphosphonofluoridate) and sarin (isopropylmethylphosphonofluoridate). Ch and acetylcholine (ACh) in blood and brain samples were analyzed using gas chromatography‐mass spectrometry methods. Net transport of Ch was determined by Ch analysis in arterial and venous samples. Unidirectional transport of [3H]Ch was determined using the indicator dilution method. During control perfusion periods of 90 min, net efflux of brain Ch occurred at a rate of 1.6 ± 0.4 nmol/g/ min, and the Ch content of the recirculated perfusate increased 10‐fold to ˜8 μM. Brain Ch content increased in proportion to the increase in perfusate Ch level, but brain ACh was unaltered. Rapid administration of soman (100 Hg) or sarin (400 μg) into the arterial perfusate after a 40‐min control period resulted in a > 10‐fold increase in ACh content in cerebral cortex, brainstem, and hippocampus.The ACh content of cerebellum increased only slightly. The Ch level in all four brain regions studied also increased two‐to fourfold above control levels. Ch efflux from brain, however, decreased to 0.2 ± 0.1 nmol/g/min during the 60 min after OP exposure. Unidirectional influx of [3H)Ch was 0.49 ± 0.07 nmol/g/min before and did not change significantly 10 or 40 min after OP exposure, thus indicating that the Ch transporter of the brain endothelial cell is not directly inhibited. Based on these results, it is proposed that (a) efflux of brain Ch occurs from the extracellular compartment, which becomes depleted when ACh breakdown is inhibited; (b) brain Ch is sequestered intracellularly; and (c) inhibition of cholinesterases by OP compounds stimulates synthesis of Ch, the source of which is not yet clear but which may involve hydrolysis of Ch‐containing brain lipids.
Neuroleptic‐Induced Supersensitivity and Brain Iron: I. Iron Deficiency and Neuroleptic‐Induced Dopamine D2 Receptor Supersensitivity
Authors: Ben‐Shachar Dorit , Youdim Moussa B. H. 
Published: October 2006

Abstract:Previous studies have shown that nutritional iron deficiency in rats reduces brain iron content, resulting in dopamine D2 receptor subsensitivity, as indicated by a decrease in [3H]spiperone binding in caudate nucleus and in behavioral responses to apomorphine. Both phenomena can be reversed by iron supplementation. The possibility that neuroleptic‐induced dopamine D2 receptor supersensitivity involves an alteration in brain iron content was investigated in nutritionally iron‐deficient and control rats chronically treated with haloperidol (5 mg/kg daily for 14 or 21 days). Neuroleptic treatment was initiated either (a) concurrently with iron deficiency or (b) 2 weeks after the start of iron deficiency. The results show that dopamine D2 receptor subsensitivity, a feature of iron deficiency, is absent in haloperidol‐treated, iron‐deficient groups. On the contrary, these animals demonstrated biochemical and behavioral dopamine D2 receptor supersensitivity that is relatively greater than that observed with control, haloperidol‐treated animals. Haloperidol (5 mg/kg daily for 21 days) as well as chlorpromazine (10 mg/kg daily for 21 days) caused a significant reduction (20–25%) in liver nonheme iron stores as compared with values in control rats. However, in iron‐deficient rats, in which liver iron stores were almost totally depleted, haloperidol had no effect. The ability of chronic haloperidol treatment to prevent the reduction of dopamine D2 receptor number during iron deficiency may be associated with alteration of body iron status. Thus, less iron may result in an increase in free haloperidol available to the dopamine D2 receptor.
4‐Aminopyridine Increases Acetylcholine Release Without Diminishing Membrane Phosphatidylcholine
Authors: Buyukuysal R. Levent , Wurtman Richard J. 
Published: October 2006

Abstract:4‐Aminopyridine (10‐4–10‐5M) increased severalfold the release of acetylcholine from rat striatal slices superfused with an eserine‐containing, choline‐free medium, and caused stoichiometric decreases in the release of choline. It had no effect on tissue acetylcholine and choline levels. Electrical stimulation of the striatal slices increased acetylcholine release without affecting that of choline. Superfusion of the stimulated slices with 4‐aminopyridine decreased choline release and increased the ratio of acetylcholine to choline in superfusates. As shown previously, electrical stimulation of the striatal slices decreased their contents of phospholipids, principally phosphatidylcholine; 4‐aminopyridine fully protected against these membrane changes. In synaptosomal preparations, 4‐aminopyridine was found to enhance the high‐affinity uptake of [14C]choline and its conversion to [14C]acetylcholine. This effect on choline uptake may underlie 4‐aminopyridine's ability to enhance acetylcholine release in the absence of supplemental choline while suppressing the “autocannibalism” of membrane phospholipids.
Intracarotid 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Administration: Biochemical and Behavioral Observations in a Primate Model of Hemiparkinsonism
Authors: Guttman Mark , Fibiger Hans C. , Jakubovic Alexander , Calne Donald B. 
Published: October 2006

Abstract:Cynomolgus monkeys received intracarotid injections of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) to produce a chronic unilateral model of parkinsonism. Extensive dopamine (DA) depletion was observed in the caudate nucleus and putamen on the side ipsilateral to the injection and this was associated with contralateral tremor, rigidity, and bradykinesia. A dose of 1.25 mg of MPTP caused ipsilateral DA loss of 99.4% in the caudate nucleus, 99.8% in the putamen, and 74.2% in the nucleus accumbens. A dose of 2.5 mg caused ipsilateral DA depletion of 99.3% in the caudate nucleus, 99.5% in putamen, and 90.1% in the nucleus accumbens. The unilateral aspect of the lesion was dose sensitive, with the 2.5‐mg dose causing bilateral asymmetric DA depletion. Tissue concentrations of serotonin were not affected by the toxin. These findings confirm that intracarotid injection of MPTP may produce a useful primate model of hemiparkinsonism that can be associated with selective unilateral DA depletion when the appropriate dose of toxin is used.
Haloperidol‐Induced Increase in Striatal Concentration of the Tripeptide, Tyr‐Gly‐Gly, Provides an Index of Increased Enkephalin Release In Vivo
Authors: Houdi Abdulghani A. , Van Loon Glen R. 
Published: October 2006

Abstract:A sensitive and specific radioimmunoassay has been developed for the tripeptide, Tyr‐Gly‐Gly, which has been shown previously to be an extraneuronal metabolite of opioid peptides derived from proenkephalin A. Using this assay, we found a regional variation in Tyr‐Gly‐Gly immunoreactivity in rat brain, with highest levels in striatum and lowest in cerebral cortex. Intracerebroventricular administration of the aminopeptidase inhibitor, bestatin, produced a threefold increase in Tyr‐Gly‐Gly immunoreactivity in rat striatum, whereas thiorphan, an enkephalinase inhibitor, produced a 45% reduction in striatal Tyr‐Gly‐Gly immunoreactivity. These data suggest that the tripeptide, Tyr‐Gly‐Gly, is in a dynamic state in the brain, and provide further support for the hypothesis that its concentration in specific brain areas may reflect the release of endogenous enkephalins in these brain areas. Further confirmation of the validity of measurements of brain Tyr‐Gly‐Gly as indices of enkephalin release under conditions of altered neuronal activity was provided by our demonstration that chronic dopamine receptor blockade with haloperidol increased striatal concentrations of both Met‐enkephalin and Tyr‐Gly‐Gly.
Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [3H]Acetylcholine Release from Rat Hippocampus
Authors: Fredholm Bertil B. 
Published: October 2006

Abstract:The inhibitory effect of an adenosine analogue, R‐N6‐phenylisopropyl adenosine (R‐PIA), of the cholinergic agonist carbachol, and of morphine on 3H efflux from [3H]choline‐labeled field‐stimulated rat hippocampal slices was compared with that produced by two inhibitors of N‐and L‐type Ca2+ channels, ω‐conotoxin (CgTx; conotoxin GVIA) and cadmium chloride. 4‐Aminopyridine (4‐AP) caused a dose‐dependent increase in evoked transmitter release, with a maximal effect (an almost threefold increase) at 100 μM. 4‐AP (100 μM) did not affect the actions of CgTx, cadmium chloride, and R‐PIA but almost abolished the effect of carbachol and morphine. The present results indicate that presynaptic muscarinic and opiate receptors reduce acetylcholine release by a mechanism that is somewhat different from that used by adenosine A1 receptors. Furthermore, the results indicate that presynaptic A1 receptors on hippocampal cholinergic neurons do not primarily regulate 4‐AP‐dependent potassium channels, but that they might act directly on a Ca2+ conductance.