Amphiphilic effects of local anesthetics on rotational mobility in neuronal and model membranes.
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.
Yun
Il
I
Department of Dental Pharmacology and Biophysics, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University, South Korea. iyun@pusan.ac.kr
Cho
Eun-Soo
ES
Jang
Hye-Ock
HO
Kim
Uk-Kyu
UK
Choi
Chang-Hwa
CH
Chung
In-Kyo
IK
Kim
Inn-Se
IS
Wood
W Gibson
WG
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects*; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D008012:Lidocaine / Q000494:pharmacology; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects*; D011318:Prilocaine / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D013229:Stearic Acids; D013748:Tetracaine / Q000494:pharmacology
D000779:Anesthetics, Local; D005456:Fluorescent Dyes; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; D013229:Stearic Acids; C026653:12-(9-anthroyloxy)stearic acid; D011318:Prilocaine; D013748:Tetracaine; D011343:Procaine; C041458:2-(9-anthroyloxy)stearic acid; D008012:Lidocaine; D002045:Bupivacaine