Depression of Phase-transition Temperature in a Model Cell Membrane by Local Anesthetics

Ueda, Issaku; Tashiro, Chikara; Arakawa, Kasumi

doi:10.1097/00000542-197705000-00004

Cited by 75 publications

(15 citation statements)

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“…We have mentioned before that neurotransmitters have been catalogued as endogenous anesthetics in living systems [30], and it is a well known fact that anesthetics depress transition phases of lipid membranes [64,65,66,67,68,69]. Therefore, our results imply the existence of such similarity: depending on the calcium and proton conditions, neurotransmitters produce in lipid membranes the same effect anesthetics do.…”

Section: Accepted Manuscriptsupporting

confidence: 62%

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

Pérez-Isidoro¹,

Ruiz‐Suárez²

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system.

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Section: Accepted Manuscriptsupporting

confidence: 62%

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

Pérez-Isidoro¹,

Ruiz‐Suárez²

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Previous studies have demonstrated that LAs interact extensively with the cell membrane. For example, LAs induce disorders among the lipid part of the cell membrane, fluidizing and expanding it by nonspecific binding (13,31). LAs raise the intracellular calcium ion level (32,33), inhibit Ca 2ϩ , Mg 2ϩ -ATPase activity (34), and reduce the mitochondrial oxidative energy metabolism (35).…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Hyperthermia-induced Apoptosis by Local Anesthetics on Human Histiocytic Lymphoma U937 Cells

Arai¹,

Kondo²,

Toko³

et al. 2002

Journal of Biological Chemistry

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The combined effects of hyperthermia at 44°C and local anesthetics on apoptosis in human histiocytic lymphoma U937 cells were investigated. When the cells were exposed to hyperthermia for l0 min marginal DNA fragmentation and nuclear fragmentation were observed. In the presence of amide-type local anesthetics further enhancement was found depending on concentration. The order of the concentration required for maximum induction was the reverse order of the lipophilicity (prilocaine > lidocaine > bupivacaine). Western blotting revealed that in hyperthermia there was initial release of Ca 2؉ from the intracellular store site as indicated by increased expression of the type 1 inositol-1,4,5-trisphosphate receptor. The effectiveness of hyperthermia combined with radiotherapy in the treatment of various solid tumors has been demonstrated (1). Furthermore, recent clinical randomized trials of patients with brain tumors, recurrent or metastatic malignant melanoma, advanced breast carcinoma, locally advanced pelvic tumors, and malignant germ cell tumors clearly have indicated the advantages for patients treated with hyperthermia combined with radiotherapy (2-6) or chemotherapy (7) compared with radiotherapy alone. However, the uniform and precise delivery of heat to tumors still remains a challenge. In many circumstances the tumor cell killing is insufficient. Drugs that have been discussed as overcoming this difficulty are heat sensitizers. An ideal sensitizer would be nontoxic at normothermia but could become cytotoxic at hyperthermic temperatures.Local anesthetics belong to a class of clinically useful compounds that exert a pharmacological effect by blocking nerve impulse propagation. The involvement of cell membranes as the site for these drug actions has been widely accepted, and many reports showing modification of cell killing due to hyperthermia by LAs 1 have been published (e.g. potentiation by procaine in murine L5178Y lymphoma cells (8) and by lidocaine in murine FM3A mammary carcinoma cells (9), potentiation of survival of tumor-bearing mice after hyperthermia combined with lidocaine (10), enhancement of hyperthermia-induced tumor regression by lidocaine in murine tumor models (11, 12), and enhancement of cytotoxic effects of hyperthermia by dibucaine, tetracaine, and procaine in hepatoma tissue culture cells (13)). However, little is known about the modification and mechanism of apoptosis when hyperthermia is combined with LAs.Here we will present our recent findings that subtoxic levels of LAs enhanced hyperthermia-induced apoptosis via the Ca 2ϩ -and mitochondria-dependent pathways in human lymphoma U937 cells. Evidence for the cardinal roles of initial release of Ca 2ϩ from intracellular store sites due to hyperthermia and the subsequent increase of [Ca 2ϩ ] i and the additional activation of the mitochondrial caspase-dependent pathway in enhancement of apoptosis induced by the combination of hyperthermia and lidocaine will also be presented. In addition the potential usefulness of LAs as sensitizers o...

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“…supports the idea that local anesthetics act rather nonspecifically and cause physical perturbations of the lipidic part of the nerve membranes, resulting in the blockade of propagation of nerve impulses. On the basis of this idea, a number of studies have been done to determine the effect of anesthetics on the phase transitions of lipid bilayers [5][6][7][8][9][10][11][12] . The depression of the phase transition temperature is often analyzed by the colligative property of bilayer membranes according to the van't Hoff model, and leads to the partition coefficients of the anesthetics into the bilayer membrane 8,10,12) .…”

Section: Introductionmentioning

confidence: 99%

Effect of a Local Anesthetic Lidocaine Hydrochloride on the Bilayer Structure of Phospholipids

et al. 2009

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Depression of Phase-transition Temperature in a Model Cell Membrane by Local Anesthetics

Cited by 75 publications

References 0 publications

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

Enhancement of Hyperthermia-induced Apoptosis by Local Anesthetics on Human Histiocytic Lymphoma U937 Cells

Effect of a Local Anesthetic Lidocaine Hydrochloride on the Bilayer Structure of Phospholipids

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