Anesthetics interacting with lipid rafts

Bandeiras, Cátia; Serro, Ana Paula; Luzyanin, Konstantin V.; Fernandes, Anabela C.; Saramago, Benilde

doi:10.1016/j.ejps.2012.10.023

Cited by 25 publications

(18 citation statements)

References 34 publications

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“…[9][10][11][12] Here we just recall that (i) the effect of anaesthetics seems to be related to the hydration of biomembranes, 13,14 (ii) effective anaesthetics (e.g. CHCl 3 ) need to be at least slightly polar to reside close to the interface of the bilayer, 3,13,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] (iii) the active molecule directly interacts with the membrane lipids and thus modifies the fluidity, the curvature and the phase structure of the bilayer which in turn alters the conformation and functional performances of ion channels, receptors and more in general of transmembrane proteins, 3,[16][17][18][19][20][21][22] and (iv) finally according to a more recent view, certain membrane proteins are clustered in cholesterol-rich ''lipid rafts'', i.e. transient micro-phase separated domains in a liquid ordered phase (L o ), with characteristics intermediate between those of a gel and of a liquid-crystalline phase, in coexistence with a fluid-like liquid disordered phase (L d ).…”

Section: Anaestheticsmentioning

confidence: 99%

Phase transitions in hydrophobe/phospholipid mixtures: hints at connections between pheromones and anaesthetic activity

Borsacchi

Geppi

Macchi

et al. 2016

Phys. Chem. Chem. Phys.

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The phase behavior of a mixture of a typical insect pheromone (olean) and a phospholipid (DOPC)/water dispersion is extensively explored through SAXS, NMR and DSC experiments. The results mimic those obtained with anaesthetics in phospholipid/water systems. They also mimic the behavior and microstructure of ternary mixtures of a membrane mimetic, bilayer-forming double chained surfactants, oils and water. Taken together with recent models for conduction of the nervous impulse, all hint at lipid involvement and the underlying unity in mechanisms of pheromone, anaesthetic and hydrophobic drugs, where a local phase change in the lipid membrane architecture may be at least partly involved in the transmission of the signal.

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Section: Anaestheticsmentioning

confidence: 99%

Phase transitions in hydrophobe/phospholipid mixtures: hints at connections between pheromones and anaesthetic activity

Borsacchi

Geppi

Macchi

et al. 2016

Phys. Chem. Chem. Phys.

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“…These local anesthetics also acted on raft-like liquid-ordered membranes, but any raft model membranes showed neither drug structure dependence nor stereoselectivity in membrane interaction, leading to the conclusion that the mechanistic relevance of membrane microdomain lipid rafts to local anesthetics is questionable at least in their effects on raft model membranes. Bandeiras et al [109] also reported that lidocaine interacted with raft model membranes, although its interactivity was weaker compared with nonraft membranes.…”

Section: Interaction Preference For Membrane Microdomain Lipid Raftsmentioning

confidence: 99%

Interaction of Local Anesthetics with Biomembranes Consisting of Phospholipids and Cholesterol: Mechanistic and Clinical Implications for Anesthetic and Cardiotoxic Effects

Tsuchiya

Mizogami

2013

Anesthesiology Research and Practice

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Despite a long history in medical and dental application, the molecular mechanism and precise site of action are still arguable for local anesthetics. Their effects are considered to be induced by acting on functional proteins, on membrane lipids, or on both. Local anesthetics primarily interact with sodium channels embedded in cell membranes to reduce the excitability of nerve cells and cardiomyocytes or produce a malfunction of the cardiovascular system. However, the membrane protein-interacting theory cannot explain all of the pharmacological and toxicological features of local anesthetics. The administered drug molecules must diffuse through the lipid barriers of nerve sheaths and penetrate into or across the lipid bilayers of cell membranes to reach the acting site on transmembrane proteins. Amphiphilic local anesthetics interact hydrophobically and electrostatically with lipid bilayers and modify their physicochemical property, with the direct inhibition of membrane functions, and with the resultant alteration of the membrane lipid environments surrounding transmembrane proteins and the subsequent protein conformational change, leading to the inhibition of channel functions. We review recent studies on the interaction of local anesthetics with biomembranes consisting of phospholipids and cholesterol. Understanding the membrane interactivity of local anesthetics would provide novel insights into their anesthetic and cardiotoxic effects.

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“…Therefore, it is also important to discuss the thermal stability of the L o phase in the presence of LAs. Differential scanning calorimetry (DSC) measurements have revealed that the thermal stabilities of the S o and L o phases are decreased by LAs [ 23 , 24 , 27 ]. Gray et al revealed that lowering the miscibility temperature, defined as the temperature for the transition between phase separation and the homogeneous phase, via the addition of liquid general anesthetics using giant plasma membrane vesicles isolated from living cells, correlates with the strength of general anesthetics [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Thermal Stability of Phase-Separated Domains in Multicomponent Lipid Membranes with Local Anesthetics

2017

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The functional mechanisms of local anesthetics (LAs) have not yet been fully explained, despite their importance in modern medicine. Recently, an indirect interaction between channel proteins and LAs was proposed as follows: LAs alter the physical properties of lipid membranes, thus affecting the channel proteins. To examine this hypothesis, we investigated changes in thermal stability in lipid membranes consisting of dioleoylphosphocholine, dipalmitoylphosphocholine, and cholesterol by adding the LAs, lidocaine and tetracaine. The miscibility temperature of liquid-ordered (Lo) and liquid-disordered (Ld) phase separation was lowered, whereas that of phase separation between solid-ordered (So) and Ld phases was unchanged by LAs. Furthermore, we measured the line tension at the Lo/Ld interface from domain boundary fluctuation and found that it was significantly decreased by LAs. Finally, differential scanning calorimetry (DSC) revealed a change in the lipid main transition temperature on the addition of LAs. Based on the DSC measurements, we considered that LAs are partitioned into two coexisting phases.

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Anesthetics interacting with lipid rafts

Cited by 25 publications

References 34 publications

Phase transitions in hydrophobe/phospholipid mixtures: hints at connections between pheromones and anaesthetic activity

Phase transitions in hydrophobe/phospholipid mixtures: hints at connections between pheromones and anaesthetic activity

Interaction of Local Anesthetics with Biomembranes Consisting of Phospholipids and Cholesterol: Mechanistic and Clinical Implications for Anesthetic and Cardiotoxic Effects

Thermal Stability of Phase-Separated Domains in Multicomponent Lipid Membranes with Local Anesthetics

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