European Journal of Pharmacology: Molecular Pharmacology最新文献

{"title":"Nitric oxide modulation of Ca2+ responses in cow tracheal epithelium","authors":"Atsushi Sakai,&nbsp;Mitsuko Kondo,&nbsp;Jun Tamaoki,&nbsp;Kimio Konno","doi":"10.1016/0922-4106(95)90079-9","DOIUrl":"10.1016/0922-4106(95)90079-9","url":null,"abstract":"<div><p>Nitric oxide (NO) plays an important role in the regulation of Ca²⁺-dependent airway epithelial function such as ciliary motility. In this experiment, the effect of NO on intracellular Ca²⁺ ([Ca²⁺]_i) was studied in cultured cow tracheal epithelium by the fura-2 method. <span><math><mtext>L</mtext><mtext>-N</mtext><msup><mi></mi><mn><mtext>G</mtext></mn></msup><mtext>-</mtext><mtext>nitroarginine</mtext></math></span> methyl ester, an NO synthase inhibitor, per se did not significantly alter baseline [Ca²⁺]_i, but bradykinin- and ATP-induced increases in [Ca²⁺]_i were significantly reduced in the presence of <span><math><mtext>L</mtext><mtext>-N</mtext><msup><mi></mi><mn><mtext>G</mtext></mn></msup><mtext>-</mtext><mtext>nitroarginine</mtext></math></span> methyl ester. This inhibitory effect disappeared by a simultaneous addition of <span>L</span>-arginine. Sodium nitroprusside or dibutyryl cyclic GMP potentiated bradykinin- and ATP-induced increases in [Ca²⁺]_i. Cytochemistry for NADPH diaphorase activity revealed the presence of NO synthase in the cultured epithelium. These results suggest that NO produced by NO synthase in airway epithelium modulates bradykinin- and ATP-induced [Ca²⁺]_i responses, which may be dependent on cyclic GMP.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 375-379"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90079-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological studies on mechanisms involved in Ca2+ oscillations in rat megakaryocytes","authors":"Chikako Uneyama ,&nbsp;Hisayuki Uneyama ,&nbsp;Michihito Takahashi ,&nbsp;Norio Akaike","doi":"10.1016/0922-4106(95)90080-2","DOIUrl":"10.1016/0922-4106(95)90080-2","url":null,"abstract":"<div><p>Extracellular application of ATP evoked the oscillatory K⁺ currents (<em>I</em>_KCa) reflecting oscillation in cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) of megakaryocyte isolated from rat bone marrow. We have reported that the [Ca²⁺]_i oscillation was regulated by intracellular Ca²⁺-pumping activity (Uneyama, H., C. Uneyama and N. Akaike, 1993, J. Biol. Chem. 268, 168). Here we found that the Ca²⁺ pump of the megakaryocyte could be divided into at least two classes according to the sensitivity to phosphorylation-modulating drugs. The effects of protein kinase C and cyclic AMP-dependent protein kinase are complementary, and the effect of Ca²⁺/calmodulin is independent of the above two kinases. In addition, this is the first report concerning the physiological regulation of Ca²⁺-ATPase in living cells.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 381-386"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90080-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of a recombinant P2Y purinoceptor","authors":"Joseph Simon ,&nbsp;Tania E. Webb ,&nbsp;Brian F. King ,&nbsp;Geoffrey Burnstock ,&nbsp;Eric A. Barnard","doi":"10.1016/0922-4106(95)90068-3","DOIUrl":"10.1016/0922-4106(95)90068-3","url":null,"abstract":"<div><p>We have previously cloned a cDNA encoding a G-protein-coupled P₂ purinoceptor from chick brain and designated this as a P_2Y1 purinoceptor (Webb, T.E., J. Simon, B.J. Krishek, A.N. Bateson, T.G. Smart, B.J. King, G. Burnstock and E.A. Barnard, 1993, FEBS Lett. 324, 219). Here, we describe the further characterisation of this recombinant receptor expressed in both simian kidney endothelial (COS-7) cells and <em>Xenopus</em> oocytes. In transfected COS-7 cell membranes, the recombinant receptor showed a high level of expression (<span><math><mtext>B</mtext><msub><mi></mi><mn><mtext>max</mtext></mn></msub><mtext> = 7.9 ± 2.2 </mtext><mtext>pmol</mtext><mtext> [</mtext><msup><mi></mi><mn>35</mn></msup><mtext>S</mtext><mtext>]</mtext><mtext>dATP</mtext><mtext>α</mtext><mtext>S bound/mg protein</mtext></math></span>) and affinity (<em>K</em>_d = 6.6 ± 0.3 nM). In these COS-7 cells, the activation of the implanted purinoceptor induced a suramin-sensitive formation of inositol 1,4,5-triphosphate (1,4,5InsP₃). Upon expression in <em>Xenopus</em> oocytes, ATP was the only natural nucleoside triphosphate to elicit a Ca²⁺-activated chloride current. The P₂ purinoceptor antagonists suramin and Reactive Blue-2 were both able to inhibit this evoked current. Utilizing both expression systems, the binding affinity profile and the functional pharmacological profile of the agonists, the common series found was: 2-methylthioATP (2-MeSATP) ⩾ ATP &gt; ADP<em>β</em>S &gt; ADP. These two agonist series and the lack of activity of adenosine, α,β-methyleneATP (α,β-meATP), 3′-<em>O</em>-(4- benzoyl)benzoyl-ATP (Bz-ATP) and UTP, together confirmed that this receptor is a specific subtype of the P_2Y purinoceptors.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 281-289"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90068-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cloning and characterization of the human GABAA receptor α4 subunit: identification of a unique diazepam-insensitive binding site","authors":"Wu Yang,&nbsp;John A. Drewe,&nbsp;Nancy C. Lan","doi":"10.1016/0922-4106(95)90072-1","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90072-1","url":null,"abstract":"<div><p>Benzodiazepines modulate γ-aminobutyric acid (GABA)-evoked chloride currents through a specific binding site at the GABA_A receptor-chloride channel complex. The heterogeneity of diazepam-sensitive benzodiazepine binding sites (type I and type II) has been identified by pharmacological approaches both with native receptors and recombinant receptors coexpressing α, β and γ subunits. In addition, two distinguishable diazepam-insensitive benzodiazepine sites arefound, spatially distributed between cerebral cortical and cerebellar regions. Coexpression of α6 with β2 and γ2L subunits creates a pharmacologically similar benzodiazepine receptor to the diazepam-insensitive site observed in cerebellum, however, there is no evidence regarding the possible subunit combination forming the DI site in cerebral tissues. Here we report the cloning of the human α4 cDNA and its pharmacology by coexpression of this α4 subunit with β2 and γ2L subunits. This recombinant receptor complex showed a high affinity for the previously described benzodiazepine partial agonist bretazenil, the pyrazoloquinoline compounds CGS-9895 and CGS-9896, as well as the inverse agonists DMCM (methyl 6,7-dimethoxy 4-ethyl-β-carboline-3-carboxylate) and Ro15-4513 as determined by [³H]Ro15-4513 binding. However, it is insensitive to the benzodiazepine type I selective compounds CL218,872 (3-methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo[4,3-<em>b</em>]pyridazine) and zolpidem as well as the benzodiazepine full agonists diazepam, halazolam and midazolam. In addition, the benzodiazepine receptor ligands DMCM, β-CCE (β-carboline-3-carboxylate ethyl ester), β-CCM (β-carboline-3-carboxylate methyl ester), FG-7142, CGS-9895 and CGS-9896 showed 7 to 10 times higher affinity for α4β2γ2L than for α6β2γ2L. The pharmacology of the α4β2γ2L receptor complex appears to resemble those of the diazepam-insensitive site found in the cerebral cortex. Our study thus suggests that this subpopulation of diazepam-insensitive GABA_A receptors may be composed of α4β2γ2L subunits.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 319-325"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90072-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71785494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and pharmacology of human GABAA receptors containing γ3 subunits","authors":"Karen L. Hadingham,&nbsp;Keith A. Wafford,&nbsp;Sally A. Thompson,&nbsp;Karan J. Palmer,&nbsp;Paul J. Whiting","doi":"10.1016/0922-4106(95)90070-5","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90070-5","url":null,"abstract":"<div><p>A cDNA encoding the γ3 subunit of the human GABA_A receptor has been obtained by molecular cloning. Its deduced amino acid sequence shows a high level of sequence identity with the published mouse and rat sequences (96%). The ligand binding pharmacology of the benzodiazepine site formed by stably-expressed human α5β3γ2S GABA_A receptor subtypes have been compared for a number of ligands. Benzodiazepine site ligands were found to be either non-selective or γ2-selective, with the exception of CL218,872, which was found to be 10-fold selective for the α5β3γ3-containing subtype. Two benzodiazepine site ligands, Rol15-4513 and FG8205 were more efficacious at α5β3β3 receptors than αβ3γ2 receptors expressed in <em>Xenopus</em> oocytes. CL218,872, which is partial agonist at α1 containing receptors, had no intrinsic activity at either α5β3γ2 or α5β3γ3. α1β2γ2S and α1β2γ3 human GABA_A receptors were also expressed in <em>Xenopus</em> oocytes and their benzodiazepine pharmacology investigated. Both in the EC₅₀ and efficacy of benzodiazepine site ligands were influence by the type of γ subunit coexpressed with α1 β2.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 301-309"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90070-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to reviewers","authors":"","doi":"10.1016/0922-4106(95)90089-6","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90089-6","url":null,"abstract":"","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 443-446"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90089-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive and negative allosteric interactions on muscarinic receptors","authors":"Lucie Hejnová ,&nbsp;Stanislav Tuček ,&nbsp;Esam E. El-Fakahany","doi":"10.1016/0922-4106(95)90085-3","DOIUrl":"10.1016/0922-4106(95)90085-3","url":null,"abstract":"<div><p>It was previously found that alcuronium increases the binding of [³H]methyl-<em>N</em>-scopolamine to cardiac muscarinic receptors by a positive allosteric action while its effect on the binding of [³H]quinuclildinyl benzilate is negative. The features of the antagonit's molecule which decide whether its allosteric interaction with alcuronium is positive or negative are not known. In the present work, it was found that alcuronium has a positive allosteric effect also on the binding [³H]atropine and [³H]methyl-<em>N</em>-piperidinyl benzilate to muscarinic receptors in rat heart atria and that its effect on the binding of [³H]methyl-<em>N</em>-quinuclidinyl benzilate is negative. A comparison of the five radiolabelld antagonists that have been investigated so far indicates that the type of allosteric interaction (positive or negative) is not determined by the presence or absence of the quaternary nitrogen or of the benzilyl moiety in the molecule of the antagonist. Apparently, features of the <em>N</em>-bearing moiety of muscarinic antagonists other than the presence of a charge on nitrogen play a key role in the determination of the type of interaction.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 427-430"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90085-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tranilast inhibits the effects of platelet-derived growth factor on cell priliferation and induction of nitric oxide","authors":"Keiichi Hishikawa ,&nbsp;Toshio Nakaki ,&nbsp;Junichi Hirahashi ,&nbsp;Takeshi Marumo ,&nbsp;Takao Saruta","doi":"10.1016/0922-4106(95)90087-X","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90087-X","url":null,"abstract":"<div><p>The effects of tranilast on DNA synthesis and cell proliferation in cultured rat mesangial cells, treated with platelet-derived growth factor (PDGF), were investigated. Tranilast significantly inhibited PDGF-stimulated DNA synthesis and cell proliferation in a dose-dependent manner. In the absence of PDGF, it also enhanced cytokine-induced nitric oxide (NO) production. PDGF significantly inhibited cytokine-induced NO production, but tranilast completely abolished this inhibitory effect of PDGF. These results show that tranilast inhibits PDGF-induced proliferation of mesangial cells under both normal and inflammatory conditions.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 435-438"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90087-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ba2+ replaces Ca2+/calmodulin in the activation of protein phosphatases and in exocytosis of all major transmitters","authors":"Matthijs Verhage ,&nbsp;Jacques J.H. Hens ,&nbsp;Pierre N.E. De Graan ,&nbsp;Frans Boomsma ,&nbsp;Victor M. Wiegant ,&nbsp;Fernando H. Lopes da Silva ,&nbsp;Willem Hendrik Gispen ,&nbsp;Wim E.J.M. Ghijsen","doi":"10.1016/0922-4106(95)90081-0","DOIUrl":"10.1016/0922-4106(95)90081-0","url":null,"abstract":"<div><p>Exocytosis from nerve terminals is triggered by depolarization-evoked Ca²⁺ entry, which also activates calmodulin and stimulates protein phosphorylation. Ba²⁺ is believed to replace Ca²⁺ in triggering exocytosis without activation of calmodulin and can therefore be used to unravel aspects of presynaptic function. We have analysed the cellular actions of Ba²⁺ in relation to its effect on transmitter release from isolated nerve terminals. Barium evoked specific release of amino acid transmitters, catecholamines and neuropeptides (EC₅₀ 0.2–0.5 mM), similar to K⁺/Ca²⁺-evoked release both in extent and kinetics. Ba²⁺- and Ca²⁺-evoked release were not additive. In contrast to Ca²⁺, Ba²⁺ triggered release which was insensitive to trifluoperizine and hardly stimulated protein phosphorylation. These observations are in accordance with the ability of Ba²⁺ to replace Ca²⁺ in exocytosis without activating calmodulin. Nevertheless, calmodulin appears to be essential for regular (Ca²⁺-triggered) exocytosis, given its sensitivity to trifluoperizine. Both Ba²⁺- and Ca²⁺-evoked release were blocked by okadaic acid. Furthermore, anti-calcineurin antibodies decreased Ba²⁺-evoked release. In conclusion, Ba²⁺ replaces Ca²⁺/calmodulin in the release of the same transmitter pool. Calmodulin-dependent phosphorylation appears not to be essential for transmitter release. Instead, our data implicate both Ca²⁺-dependent and -independent <em>de</em>phosphorylation in the events prior to neurotransmitter exocytosis.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 387-398"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90081-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary adenylate cyclase-activating polypeptide stimulates cardiodilatin/atrial natriuretic peptide (CDD/ANP-(99–126) secretion from cultured neonatal rat myocardiocytes","authors":"Iris Bäsler ,&nbsp;Michaela Kuhn ,&nbsp;Werner Müller ,&nbsp;Wolf-Georg Forssmann","doi":"10.1016/0922-4106(95)90074-8","DOIUrl":"10.1016/0922-4106(95)90074-8","url":null,"abstract":"<div><p>It has been reported that the highly homologous neuropeptides pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP) exert similar cardiovascular effects in vivo. In the present study we compared the effects of these neuropeptides on myocardial cyclic AMP content and the release of immunoreactive CDD/ANP-(99–126) (atrial natriuretic peptide). In cultured neonatal rat cardiomyocytes PACAP and VIP evoke concentration-dependent increases in intracellular cyclic AMP content but responses to VIP are markedly less. PACAP stimulates the release of CDD/ANP-(99–126) in a concentration-dependent manner with a threshold concentration of 1 nM, and up to a 6-fold increase in basal secretion at 1 μM PACAP. In contrast, VIP had no effect on the release of CDD/ANP. Pretreatment of cells with the competitive PACAP-antagonist, PACAP-6-38 (1 μM), significantly reduces the effects of PACAP on intracellular cyclic AMP and on CDD/ANP-(99–126) secretion and abolishes the effects of VIP on cyclic AMP. Pretreatment with VIP-receptor antagonist (1 μM) prevents the cyclic AMP-responses to VIP while increases in cyclic AMP as well as stimulation of CDD/ANP-(99–126) release by PACAP are not affected. It is concluded that both neuropeptides directly influence cardiac myocytes through an increase in intracellular cyclic AMP. Release of CDD/ANP-(99–126) by PACAP may be involved in the decrease in blood pressure that follows intravenous administration of this peptide. The higher potency of PACAP to induce cyclic AMP synthesis, its stimulating effect on the release of CDD/ANP-(99–126) and the finding that the VIP-receptor antagonist inhibits responses to VIP but not to PACAP suggest that PACAP activates cardiac myocytes through a PACAP-specific receptor.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 335-342"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90074-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}