Activation of neuronal N-methyl-D-aspartate receptor channels by lipid emulsions.
Lipid emulsions are widely used as carriers for hypnotics such as propofol, etomidate, and diazepam. It is assumed that the emulsions alone exert no effect on cellular functions nor influence the pharmacokinetics, pharmacodynamics, or anesthetic and analgetic potency of the hypnotics they carry. To elucidate possible interactions between lipid emulsions and cell membranes, in particular membrane-bound proteins, we investigated the effects of commercially available lipid emulsions on the cell membranes of cultured cortical neurons from the mouse by using the whole-cell configuration of the patch-clamp technique. Of nine lipid emulsions tested, three, i.e., Intralipid, Structolipid, and, to a much lesser extent, Abbolipid, activated membrane currents in the neuronal cells in a dilution-dependent manner. The emulsion-induced currents were not affected by picrotoxin or bicuculline but were inhibited by DL-AP5 and ketamine. The voltage dependence of the currents was influenced by the presence of Mg(2+) in a way that is typical for currents conducted by N-methyl-D-aspartate receptor channels. We conclude that Intralipid, Structolipid, and Abbolipid activate N-methyl-D-aspartate receptor channels in cortical neurons.


CONCLUSIONS
Lipid emulsions are widely used as carriers for hypnotics such as propofol, etomidate, or diazepam. We tested nine commercially available lipid emulsions and demonstrate that three of them--Intralipid, Structolipid, and Abbolipid--activate NMDA receptor channels in the membranes of cortical neuronal cells.
Weigt
Henry U
HU
University Clinic of Anesthesiology, Ulm, Germany.
Georgieff
Michael
M
Beyer
Cordian
C
Föhr
Karl J
KJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004337:Drug Carriers / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline; D004337:Drug Carriers; D005217:Fat Emulsions, Intravenous; D018756:GABA Antagonists; D007473:Ion Channels; D016202:N-Methylaspartate; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate