Effect of multiple serine/alanine mutations in the transmembrane spanning region V of the D2 dopamine receptor on ligand binding.

Abstract:

:Three conserved serine residues (Ser193, Ser194, and Ser197) in transmembrane spanning region (TM) V of the D2 dopamine receptor have been mutated to alanine, individually and in combination, to explore their role in ligand binding and G protein coupling. The multiple Ser -->Ala mutations had no effect on the binding of most antagonists tested, including [3H]spiperone, suggesting that the multiple mutations did not affect the overall conformation of the receptor protein. Double or triple mutants containing an Ala197 mutation showed a decrease in affinity for domperidone, whereas Ala193 mutants showed an increased affinity for a substituted benzamide, remoxipride. However, dopamine showed large decreases in affinity (>20-fold) for each multiple mutant receptor containing the Ser193Ala mutation, and the high-affinity (coupled) state of the receptor (in the absence of GTP) could not be detected for any of the multiple mutants. A series of monohydroxylated phenylethylamines and aminotetralins was tested for their binding to the native and multiple mutant D2 dopamine receptors. The results obtained suggest that Ser193 interacts with the hydroxyl of S-5-hydroxy-2-dipropylaminotetralin (OH-DPAT) and Ser197 with the hydroxyl of R-5-OH-DPAT. We predict that Ser193 interacts with the hydroxyl of R-7-OH-DPAT and the 3-hydroxyl (m-hydroxyl) of dopamine. Therefore, the conserved serine residues in TMV of the D2 dopamine receptor are involved in hydrogen bonding interactions with selected antagonists and most agonists tested and also enable agonists to stabilise receptor-G protein coupling.

journal_name

J Neurochem

authors

Coley C,Woodward R,Johansson AM,Strange PG,Naylor LH

doi

10.1046/j.1471-4159.2000.0740358.x

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

358-66

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

74

pub_type

杂志文章
  • Active uptake of substance P carboxy-terminal heptapeptide (5-11) into rat brain and rabbit spinal cord slices.

    abstract::We previously reported that nerve terminals and glial cells lack an active uptake system capable of terminating transmitter action of substance P (SP). In the present study, we demonstrated the existence of an active uptake system for SP carboxy-terminal heptapeptide, (5-11)SP. When the slices from either rat brain or...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb06323.x

    authors: Nakata Y,Kusaka Y,Yajima H,Segawa T

    更新日期:1981-12-01 00:00:00

  • Effects of chronic ethanol consumption and aging on dopamine, serotonin, and metabolites.

    abstract::This study examined the hypothesis that chronic ethanol consumption results in significant abnormalities in both the dopaminergic and the serotonergic system of aged rats. Levels of dopamine (DA), serotonin [5-hydroxytryptamine (5-HT)], 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindole-3-acetic acid (5-HIAA)...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.66052168.x

    authors: Woods JM,Druse MJ

    更新日期:1996-05-01 00:00:00

  • Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95.

    abstract::Semaphorins are a family of secreted and membrane-associated proteins involved in growth cone guidance during development. Here, we describe the interaction of Semaphorin4F (Sema4F) with the post-synaptic density protein SAP90/PSD-95. Using the yeast two-hybrid system and coprecipitation assays we were able to show an...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2001.00447.x

    authors: Schultze W,Eulenburg V,Lessmann V,Herrmann L,Dittmar T,Gundelfinger ED,Heumann R,Erdmann KS

    更新日期:2001-08-01 00:00:00

  • Regional differences in the capacity for ammonia removal by brain following portocaval anastomosis.

    abstract::Portocaval anastomosis (PCA) in the rat leads, within 4 weeks, to severe liver atrophy, sustained hyperammonemia, and increased brain ammonia. Because brain is not equipped with an effective urea cycle, removal of ammonia involves glutamine synthesis and PCA results in significantly increased brain glutamine. Glutamin...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1988.tb01064.x

    authors: Butterworth RF,Girard G,Giguère JF

    更新日期:1988-08-01 00:00:00

  • The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function.

    abstract::Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson's disease-like pathology. To begin to address ho...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12231

    authors: Levesque S,Taetzsch T,Lull ME,Johnson JA,McGraw C,Block ML

    更新日期:2013-06-01 00:00:00

  • Correlation between 2',3'-cyclic nucleotide 3'-phosphohydrolase activity and demyelination in vitro using a syngeneic system.

    abstract::Cultures of myelinated SJL/J fetal mouse spinal cord were incubated with serum and lymphoid cells from syngeneic animals with experimental allergic encephalomyelitis (EAE) induced by syngeneic spinal cord homogenate (SSCH) in complete Freund's adjuvant or others injected with complete Freund's adjuvant alone. After 24...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1985.tb05462.x

    authors: Roth GA,Bornstein MB,Röyttä M,Lyman WD,Raine CS

    更新日期:1985-02-01 00:00:00

  • Regulation of neuropeptide Y release by neuropeptide Y receptor ligands and calcium channel antagonists in hypothalamic slices.

    abstract::Neuropeptide Y (NPY) is an important regulator of energy balance in mammals through its orexigenic, antithermogenic, and insulin secretagogue actions. We investigated the regulation of endogenous NPY release from rat hypothalamic slices by NPY receptor ligands and calcium channel antagonists. High-potassium stimulatio...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1999.0730641.x

    authors: King PJ,Widdowson PS,Doods HN,Williams G

    更新日期:1999-08-01 00:00:00

  • Novel opioid peptide amidorphin: characterization and distribution of amidorphin-like immunoreactivity in bovine, ovine, and porcine brain, pituitary, and adrenal medulla.

    abstract::We have recently isolated from bovine adrenal medulla a novel C-terminally amidated opioid peptide, amidorphin, which derives from proenkephalin A. Amidorphin revealed a widespread distribution in bovine, ovine, and porcine tissue. Particularly high concentrations of amidorphin immunoreactivity were detected in adrena...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1985.tb07218.x

    authors: Liebisch DC,Seizinger BR,Michael G,Herz A

    更新日期:1985-11-01 00:00:00

  • Modulation of retinal aromatic L-amino acid decarboxylase via alpha 2 adrenoceptors.

    abstract::Aromatic L-amino acid decarboxylase (AAAD) activity of the rat retina increases when animals are placed in a lighted environment from the dark. The rise of activity can be inhibited by administering alpha 2 adrenoceptor agonists. In the dark, the enzyme activity can be made to increase by administering alpha 2 adrenoc...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1989.tb09169.x

    authors: Rossetti Z,Krajnc D,Neff NH,Hadjiconstantinou M

    更新日期:1989-02-01 00:00:00

  • Retinoic acid- and phorbol ester-induced neuronal differentiation down-regulates caveolin expression in GnRH neurons.

    abstract::GN11 and GT1-7 are immortalized gonadotropin-releasing hormone-positive murine cell lines exhibiting the features of immature olfactory neurons and differentiated hypothalamic neurons, respectively. Using electron microscopy and biochemical assays (RT-PCR and immunoblotting) we determined the presence of numerous cave...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2007.05109.x

    authors: D'Orlando C,Guzzi F,Gravati M,Biella G,Toselli M,Meneveri R,Barisani D,Parenti M

    更新日期:2008-03-01 00:00:00

  • Proteasomal inhibition leads to formation of ubiquitin/alpha-synuclein-immunoreactive inclusions in PC12 cells.

    abstract::Proteasomal dysfunction has been recently implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease and diffuse Lewy body disease. We have developed an in vitro model of proteasomal dysfunction by applying pharmacological inhibitors of the proteasome, lactacystin or ZIE[O-tBu]...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2001.00474.x

    authors: Rideout HJ,Larsen KE,Sulzer D,Stefanis L

    更新日期:2001-08-01 00:00:00

  • Pre- and early postnatal enriched environmental experiences prevent neonatal hypoxia-ischemia late neurodegeneration via metabolic and neuroplastic mechanisms.

    abstract::Prenatal and early postnatal periods are important for brain development and neural function. Neonatal insults such as hypoxia-ischemia (HI) causes prolonged neural and metabolic dysregulation, affecting central nervous system maturation. There is evidence that brain hypometabolism could increase the risk of adult-ons...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.15221

    authors: Durán-Carabali LE,Kawa Odorcyk F,Greggio S,Teribele Venturin G,Farias Sanches E,Garcia Schu G,Soares Carvalho A,Avila Pedroso T,de Sá Couto-Pereira N,Costa da Costa J,Dalmaz C,Rigon Zimmer E,Netto CA

    更新日期:2020-10-23 00:00:00

  • Neuro-inflammation induced in the hippocampus of 'binge drinking' rats may be mediated by elevated extracellular glutamate content.

    abstract::The neuropathological and immune changes induced in the brain by 'binge drinking' have been investigated in a rat model. Evidence of neuro-inflammation was identified in the 'binge drinking' rat model of alcohol abuse after 3 weeks of administration of 2 or 3 g/kg ethanol (EtOH), three times per day for two consecutiv...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2009.06389.x

    authors: Ward RJ,Colivicchi MA,Allen R,Schol F,Lallemand F,de Witte P,Ballini C,Corte LD,Dexter D

    更新日期:2009-12-01 00:00:00

  • Hypoxia-inducible factor-1α mediates up-regulation of neprilysin by histone deacetylase-1 under hypoxia condition in neuroblastoma cells.

    abstract::Hypoxia-inducible factor (HIF)-1 is the key transcriptional activator mediating both adaptive and pathological responses to hypoxia. The purpose of this study was to find the role of HIF-1 in regulating neprilysin (NEP) at the early stage of hypoxia and explore the underlying mechanism. In this study, we demonstrated ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12795

    authors: Wang H,Sun M,Yang H,Tian X,Tong Y,Zhou T,Zhang T,Fu Y,Guo X,Fan D,Yu A,Fan M,Wu X,Xiao W,Chui D

    更新日期:2014-10-01 00:00:00

  • Pre-synaptic dopamine D(3) receptor mediates cocaine-induced structural plasticity in mesencephalic dopaminergic neurons via ERK and Akt pathways.

    abstract::Exposure to psychostimulants results in neuroadaptive changes of the mesencephalic dopaminergic system including morphological reorganization of dopaminergic neurons. Increased dendrite arborization and soma area were previously observed in primary cultures of mesencephalic dopaminergic neurons after 3-day exposure to...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2011.07618.x

    authors: Collo G,Bono F,Cavalleri L,Plebani L,Merlo Pich E,Millan MJ,Spano PF,Missale C

    更新日期:2012-03-01 00:00:00

  • Increased caspase activation and decreased TDP-43 solubility in progranulin knockout cortical cultures.

    abstract::Null mutations in progranulin (GRN) are associated with frontotemporal lobar degeneration characterized by intraneuronal accumulation of TAR DNA-binding protein-43 (TDP-43). However, the mechanism by which GRN deficiency leads to neurodegeneration remains largely unknown. In primary cortical neurons derived from Grn k...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2010.06961.x

    authors: Kleinberger G,Wils H,Ponsaerts P,Joris G,Timmermans JP,Van Broeckhoven C,Kumar-Singh S

    更新日期:2010-11-01 00:00:00

  • A unique snake venom neuritogenesis mechanism: A cornerstone in the treatment of neurodegenerative diseases?: An Editorial Highlight for "Transcriptomic, proteomic, and biochemical analyses reveal a novel neuritogenesis mechanism of Naja naja venom α-elap

    abstract::Neurodegenerative diseases are a worldwide health problem and are a major cause of death and disability. A progressive loss of defined neuronal populations is triggered by a diverse array of stimuli that converge in deficient neurotrophic signaling. Therefore, much effort has been placed in recent years in the charact...

    journal_title:Journal of neurochemistry

    pub_type: 社论

    doi:10.1111/jnc.15196

    authors: Hernández-Kelly LC,Ortega A

    更新日期:2020-10-19 00:00:00

  • Photoreceptor-specific expression, light-dependent localization, and transcriptional targets of the zinc-finger protein Yin Yang 1 in the chicken retina.

    abstract::The zinc-finger transcription factor Yin Yang 1 (YY1) is a multifunctional protein that plays a critical role in embryonic development. Although it has been shown to play a role in eye development, its expression in the retina was not previously described. Here, we investigated YY1 expression in chicken tissues and we...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2007.05150.x

    authors: Bernard M,Voisin P

    更新日期:2008-05-01 00:00:00

  • Regulation of alpha2A-adrenergic receptor expression by epinephrine in cultured astroglia from rat brain.

    abstract::Epinephrine (Epi) mediates various physiological effects via alpha2A-adrenergic receptors (alpha2A-ARs). Studies in mice with a point mutation in the gene for alpha2A-AR have shown that these receptors are responsible for the centrally mediated depressor effects of alpha2-AR agonists. These studies underscore the impo...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1998.70010086.x

    authors: Reutter MA,Richards EM,Sumners C

    更新日期:1998-01-01 00:00:00

  • Functional effects of tau gene mutations deltaN296 and N296H.

    abstract::Mutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP-17). Functionally, about half of the known mutations increase the alternative mRNA splicing of exon 10 of the tau gene, resulting in the overproduction of tau isoforms with four microtubule-binding repeats. The other...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.0022-3042.2001.00729.x

    authors: Yoshida H,Crowther RA,Goedert M

    更新日期:2002-02-01 00:00:00

  • Studies on a possible functional coupling between presynaptic acetylcholinesterase and high-affinity choline uptake in the rat brain.

    abstract::The relationships between presynaptic acetylcholinesterase (AChE) and high-affinity choline uptake (HACU) were investigated using a monolayer of rat cortex synaptosomes in superfusion conditions. The following sets of experiments were performed: determination of [3H]choline ([3H]Ch) uptake during superfusion with [3H]...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1986.tb13076.x

    authors: Raiteri M,Marchi M,Caviglia AM

    更新日期:1986-12-01 00:00:00

  • Direct cytotoxicity of ethylcholine mustard aziridinium in cerebral microvascular endothelial cells.

    abstract::The choline analogue ethylcholine mustard aziridinium (AF64A) is a potent and irreversible inhibitor of choline uptake in brain synaptosomes and is used as a neurotoxin to produce animal models of cholinergic hypofunction. However, previous studies have shown that intraocular administration of AF64A in rats not only r...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1993.tb03318.x

    authors: Gómez C,Martín C,Galea E,Estrada C

    更新日期:1993-04-01 00:00:00

  • Involvement of Src kinase in T-type calcium channel-dependent neuronal differentiation of NG108-15 cells by hydrogen sulfide.

    abstract::Hydrogen sulfide (H(2)S), a gasotransmitter, induces neuronal differentiation characterized by neuritogenesis and functional up-regulation of high voltage-activated Ca(2+) channels, via activation of T-type Ca(2+) channels in NG108-15 cells. We thus analyzed signaling mechanisms for the H(2)S-evoked neuronal different...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2010.06774.x

    authors: Tarui T,Fukami K,Nagasawa K,Yoshida S,Sekiguchi F,Kawabata A

    更新日期:2010-07-01 00:00:00

  • Inability of [125I]Sar1, Ile8-angiotensin II to move between the blood and cerebrospinal fluid compartments.

    abstract::The angiotensin II competitive antagonist [125I]-Sar1, Ile8-angiotensin II was not transported from the vascular space to the cerebroventricular space in either intact or nephrectomized rats. In addition [125I]Sar1, Ile8-angiotensin II lacked the capacity to move in the opposite direction over a 20-min collection peri...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1988.tb02946.x

    authors: Harding JW,Sullivan MJ,Hanesworth JM,Cushing LL,Wright JW

    更新日期:1988-02-01 00:00:00

  • Production of platelet-activating factor from rat cerebellar granule cells in culture.

    abstract::Platelet-activating factor (PAF) is a potent lipid mediator implicated in various pathological conditions, including CNS neuronal injury. However, the production of PAF by mammalian CNS neurons has not as yet been demonstrated. In the present study, we demonstrate that PAF is produced by cultured rat cerebellar granul...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1990.tb01239.x

    authors: Yue TL,Lysko PG,Feuerstein G

    更新日期:1990-05-01 00:00:00

  • Kinetic effects of terbium ions on muscarinic acetylcholine receptors of murine neuroblastoma cells.

    abstract::Preincubation of murine neuroblastoma cells (clone N1E-115) with terbium chloride resulted in a significant potentiation of carbachol-mediated increase in cyclic GMP formation. This effect was accompanied by a shift of the peak response from 30 s to 120 s and a 6-fold decrease in carbachol concentration producing half...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1984.tb02760.x

    authors: El-Fakahany EE,Pfenning M,Richelson E

    更新日期:1984-03-01 00:00:00

  • Extracellular glutamate is increased in thalamus during thiamine deficiency-induced lesions and is blocked by MK-801.

    abstract::The current study measured extracellular fluid (ECF) levels of excitatory amino acids before and during the onset of thiamine deficiency-induced pathologic lesions. Male Sprague-Dawley rats were treated with daily pyrithiamine (0.25 mg/kg i.p.) and a thiamine-deficient diet (PTD). Microdialysates were simultaneously c...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1993.tb07457.x

    authors: Langlais PJ,Zhang SX

    更新日期:1993-12-01 00:00:00

  • An apparent paradox in the occurrence, and the in vivo turnover, of C-terminal tyrosine in membrane-bound tubulin of brain.

    abstract::Tubulin tyrosine ligase catalyzes the reversible addition of tyrosine to the C-terminus of tubulin alpha chains. By using ligase and carboxypeptidase A in conjunction, we have previously shown that brain cytoplasmic tubulin exists in three forms: 15-40% already has C-terminal tyrosine, another 10-30% can accept additi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1980.tb03708.x

    authors: Nath J,Flavin M

    更新日期:1980-09-01 00:00:00

  • Analysis of human neuropeptide FF gene expression.

    abstract::As an initial step to study the function of the gene encoding the human neuropeptide FF (NPFF), we cloned a 4.7-kb sequence from the promoter region. Primer extension and 5'-rapid amplification of cDNA ends revealed multiple transcription initiation sites. Northern blot analysis of the mRNA expression revealed a speci...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2002.01035.x

    authors: Nystedt JM,Brandt AM,Mandelin J,Vilim FS,Ziff EB,Panula P

    更新日期:2002-09-01 00:00:00

  • Phosphodiesterase isoform-specific expression induced by traumatic brain injury.

    abstract::Traumatic brain injury (TBI) results in significant inflammation which contributes to the evolving pathology. Previously, we have demonstrated that cyclic AMP (cAMP), a molecule involved in inflammation, is down-regulated after TBI. To determine the mechanism by which cAMP is down-regulated after TBI, we determined wh...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12049

    authors: Oliva AA Jr,Kang Y,Furones C,Alonso OF,Bruno O,Dietrich WD,Atkins CM

    更新日期:2012-12-01 00:00:00