Effects of Local Anesthetics on the Fluidity of Synaptosomal Plasma Membrane Vesicles Isolated from Bovine Brain
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국소마취제의 약리학적 작용기전을 탐구키 위하여 소의 신선한 대뇌피질로부터 synaptosomal plasma membrane vesicles(SPMV)를 분리한 후 그 소수성 중심부의 microviscosity에 미치는 국소마취제의 영향을 pyrene 형광 probe법으로 측정한 결과 lidocaine HCI과 procaine HCI이 microviscosity를 낮춘다는 것을 알았고 그 정도는 procaine HCI에 비하여 tidocaine.HCI이 더욱 컸다. 또 국소마취 제 가 dimyristoylphosphatidylcholine (DMPC) multilamellar liposomes의 상전 이온도를 낮추며 cooperative unit크기를 감소시킨다는 것도 시차 열량분석법으로 알게 되었다. 상전이온도와 cooperative unit 크기의 감소 정도는 dibucaine HCI>tetracaine HCI>lidocaine HCI > procaine HCI의 순이었다. 【To elucidate the mechanism of action of local anesthetics, the effects of local anethetics on the microenvironment of the lipid bilayers of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine brain and dimyristoylphosphatidylcholine (DMPC) multilamellar liposomes were investigated employing the intermolecular excimer fluorescence technique and differential scanning calorimetry (DSC). The relative intensities of excimer and monomer fluorescence of pyrene are a simple linear function of the viscosity of a homologous series of solvents. The microviscosity( ${\eta}$ )of the hydrocarbon region of SPMV was measured by this method and the value was $57.3{\pm}5.3\;cP$ at $37^{\circ}C$ . In the presence of lidocaine-HCl and procaine-HCl, the values decreased to $46.5{\pm}5.1\;cP$ and $54.7{\pm}4.8\;cP$ , respectvely. The differential scanning thermograms of DMPC multilamellar liposomes showed that local anesthetics significantly lowered the phase transition temperature, broadened the thermogram peaks, and reduced the size of the cooperative unit. These results indicate that local anesthetics have significant fluidizing effects on biomembranes and perturbation of membrane lipids may produce some, but not all, of their pharmacological actions.】Keywords:
Microviscosity
Tetracaine
Dibucaine
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The fluorescence polarization of a fluorescence probe embedded in vesicle bilayers was assessed for dicarboxylic acid surfactant/dimyristoyl phosphatidylcholine (DMPC) mixtures. The effects of additive surfactants on membrane fluidity were investigated. Simultaneously, mixed vesicles size was estimated from light scattering and vesicle formation was confirmed by electron microscopic observation. With increase in hydrocarbon chain length of additive surfactants, transition temperature of membrane fluidity increased. The transition temperature rose in an order, N-acyl-L-aspartic acid (CnAsp) /DMPC, alkenylsuccinic acid (CnSA) /DMPC, and fatty acid/DMPC systems. For the C14SA/DMPC mixed system, size was not affected by mole fraction of a surfactant, while transition temperature varied with the addition of C14SA. For the C12Asp/DMPC system, transition temperature showed no change but particle size remarkably decreased with mole fraction.
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Impulse block by LA occurs through the inhibition of voltage-gated Na+ channels. Both protonated and neutral LAs can inhibit Na+ channels though interference with the conformational changes that underly the activation process (the sequence of events that occurs as channels progress from the closed resting state to the open conducting state). The occlusion of open channels contributes little to the overall inhibition. Local anesthetic inhibition of Na+ currents increases with repetitive depolarizations in a process called phasic block. Phasic block represents increased LA binding, either because more channels become accessible during depolarization or because the channel conformations favored by depolarization bind LA with higher affinity. The details of phasic block are dependent on LA chemistry: certain LAs bind and dissociate quite rapidly, others act more slowly; some LAs interact effectively with closed states that occur intermediately between resting and open states, others favor the open channel, and still others have a higher affinity for inactivated states. Channel activation accelerates LA binding, and LAs may bind more tightly to activated and inactivated than to resting channels. In this regard, both the modulated receptor and the guarded receptor hypotheses are valid. In binding to activated and inactivated channels, LAs prevent the conformational changes of activation and antagonize the binding of activator agents that poise channels in activated, open states. These reciprocal actions are one aspect of the concerted conformational rearrangements that occur throughout Na+ channels during gating. The LA binding site may exist in the channel's pore, at the membrane-protein interface, or within the protein subunits of the channel. Judging from its susceptibility to intracellular proteases and its accessibility to LAs with limited membrane permeability (i.e., quaternary LAs in the cytoplasm), the site lies nearer to the cytoplasmic than the external surface of the membrane. Nevertheless, protons in the external medium influence the dissociation of LA from the closed channel. Binding of LAs at the inhibitory site is weak and loose. If one accounts for the membrane-concentrating effects of LA hydrophobicity that are expressed as membrane: buffer partition coefficients equal to 10(2)-10(4), then the apparent LA affinities are low. The equilibrium dissociation constants calculated on the basis of free drug in the membrane are 1-10 mM, with a correspondingly weak binding to the inhibitory LA site. The stereospecificity of LA action is also relatively nonselective, suggesting a loose fit between ligand and binding site.(ABSTRACT TRUNCATED AT 400 WORDS)
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Since 1922 when Wu proposed the use of the Folin phenol reagent for the measurement of proteins (l), a number of modified analytical procedures ut.ilizing this reagent have been reported for the determination of proteins in serum (2-G), in antigen-antibody precipitates (7-9), and in insulin (10).Although the reagent would seem to be recommended by its great sensitivity and the simplicity of procedure possible with its use, it has not found great favor for general biochemical purposes.In the belief that this reagent, nevertheless, has considerable merit for certain application, but that its peculiarities and limitations need to be understood for its fullest exploitation, it has been studied with regard t.o effects of variations in pH, time of reaction, and concentration of reactants, permissible levels of reagents commonly used in handling proteins, and interfering subst.ances.Procedures are described for measuring protein in solution or after precipitation wit,h acids or other agents, and for the determination of as little as 0.2 y of protein. MethodReagents-Reagent A, 2 per cent N&OX in 0.10 N NaOH.Reagent B, 0.5 per cent CuS04.5Hz0 in 1 per cent sodium or potassium tartrabe.Reagent C, alkaline copper solution.Mix 50 ml. of Reagent A with 1 ml. of Reagent B. Discard after 1 day.Reagent D, carbonate-copper solution, is the same as Reagent C except for omission of NaOH.Reagent E, diluted Folin reagent.Titrate Folin-Ciocalteu phenol reagent ((II), Eimer and Amend, Fisher Scientific Company, New York) with NaOH t.o a phenolphthalein end-point.On the basis of this titration dilute the Folin reagent (about 2-fold) to make it 1 N in acid.Working standards may be prepared from human serum diluted IOO-to lOOO-fold (approximately 700 to 70 y per ml.).These in turn may be checked against a standard solution of crystalline bovine albumin (Armour and
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The inhibition of sodium currents by quaternary derivatives of lidocaine was studied in single myelinated nerve fibers. Membrane currents were diminished little by external quaternary lidocaine (QX). QX present in the axoplasm (<0.5 mM) inhibited sodium currents by more than 90%. Inhibition occurred as the sum of a constant, tonic phase and a variable, voltage-sensitive phase. The voltage-sensitive inhibition was favored by the application of membrane potential patterns which produce large depolarizations when sodium channels are open. Voltage-sensitive inhibition could be reversed by small depolarizations which opened sodium channels. One explanation of this observation is that QX molecules enter open sodium channels from the axoplasmic side and bind within the channels. The voltage dependence of the inhibition by QX suggests that the drug binds at a site which is about halfway down the electrical gradient from inside to outside of the sodium channel.
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ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Stable Reagent for the Liebermann-Burchard Reaction. Application to Rapid Serum Cholesterol DeterminationT. C. Huang, C. P. Chen, Verna. Wefler, and Alan. RafteryCite this: Anal. Chem. 1961, 33, 10, 1405–1407Publication Date (Print):September 1, 1961Publication History Published online1 May 2002Published inissue 1 September 1961https://pubs.acs.org/doi/10.1021/ac60178a040https://doi.org/10.1021/ac60178a040research-articleACS PublicationsRequest reuse permissionsArticle Views797Altmetric-Citations408LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
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ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharged anesthetics selectively alter plasma membrane orderWilliam D. Sweet, W. Gibson Wood, and Friedhelm SchroederCite this: Biochemistry 1987, 26, 10, 2828–2835Publication Date (Print):May 19, 1987Publication History Published online1 May 2002Published inissue 19 May 1987https://pubs.acs.org/doi/10.1021/bi00384a026https://doi.org/10.1021/bi00384a026research-articleACS PublicationsRequest reuse permissionsArticle Views58Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
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