Amphiphilic effects of local anesthetics on rotational mobility in neuronal and model membranes

Abstract

To provide a basis for studying the molecular mechanism of pharmacological action of local anesthetics, we carried out a study of the membrane actions of tetracaine, bupivacaine, lidocaine, prilocaine and procaine. Fluorescence polarization of 12-(9-anthroyloxy)stearic acid (12-AS) and 2-(9-anthroyloxy)stearic acid (2-AS) were used to examine the effects of local anesthetics on differential rotational mobility between polar region and hydrocarbon interior of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. The two membrane components differed with respect to 2 and 12 anthroyloxy stearate (2-AS, 12-AS) probes, indicating that a difference in the membrane fluidity may be present. In a dose-dependent manner, tetracaine, bupivacaine, lidocaine, prilocaine and procaine decreased anisotropy of 12-AS in the hydrocarbon interior of the SPMV, SPMVTL and SPMVPL, but tetracaine, bupivacaine, lidocaine and prilocaine increased anisotropy of 2-AS in the membrane interface. These results indicate that local anesthetics have significant disordering effects on hydrocarbon interior of the SPMV, SPMVTL and SPMVPL, but have significant ordering effects on the membrane interface, and thus they could affect the transport of Na(+) and K(+) in nerve membranes, leading to anesthetic action.

Drinking-Related Tetrahydroharmans Counteract the Membrane Effects of Local Anesthetic Lidocaine

“…Lidocaine induces larger fluidity changes in DPPC membranes than in POPC/cholesterol membranes, suggesting that membrane fluidization depends on the lipid composition. Its membrane effects are consistent with the previous reports of local anesthetics to fluidize artificial and synaptosomal membranes [33,40]. The membrane-acting concentrations (0.1-2 mg/mL) of lidocaine are lower than or almost correspond to its clinically used concentrations.…”

“…Besides voltage-gated sodium channels of neural and cardiac cells, local anesthetics act on membrane lipids to modify the physicochemical properties like fluidity of artificial and biological membranes, thereby directly affecting the function of biomembranes and indirectly modulating the activity of ion channels through the conformational changes of transmembrane proteins [40]. Drug-induced membrane fluidization is referred to as one of pharmacological mechanisms for local anesthetics [34].…”

Interaction of Serotonin1AReceptors from Bovine Hippocampus with Tertiary Amine Local Anesthetics

“…This indicates a decrease in the rotational mobility of the fluorescent probe in the headgroup region of the membrane. Earlier reports have described membrane perturbing effects of the local anesthetics in relation to their anesthetic action (Sweet and Schroeder, 1986;Yun et al, 2002). However, while all the four local anesthetics affect the ligand binding and G-protein coupling of the serotonin 1A receptor, only tetracaine and dibucaine are found to alter the fluidity of the membrane, indicating that one cannot exclude a role for the membrane environment in the action of local anesthetics.…”

“…Moreover, one of us has previously shown that stress such as heat shock can induce anisotropic changes in membrane fluidity, i.e., the change in membrane fluidity was different when monitored in different regions in adult rat liver cells (Revathi et al, 1994). Interestingly, such depth-dependent modulation of membrane fluidity induced by alcohols (Kitagawa and Hirata, 1992) and local anesthetics (Yun et al, 2002) has also been reported. It is for this reason that we employed three fluorescent probes NBD-PE, TMA-DPH, and DPH to assess the fluidity changes induced by local anesthetics in this study.…”

Aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade de brometos de amônio quaternários estruturalmente análogos a procaína, com atividade de bloqueio da transmissão neuromuscular, para estudos de <i>(Q)SAR</i>

“…Sugere-se que estes compostos se ligam a um sítio específico do canal iônico, induzindo uma mudança de conformação no receptor nicotínico, fechando-o ou impedindo a sua ativação (consequentemente inibindo o fluxo de íons pelo canal) (Yun et al, 2002;Weizenmann et al, 2012).…”