Anesthetics modulate phospholipase C hydrolysis of monolayer phospholipids by surface pressure.
Anesthetics are believed to produce anesthesia through the reversible inhibition of synaptic transmission but how this is accomplished is unknown. Based on earlier studies of anesthetic-enzyme-phospholipid interaction, we surmised that anesthetics may inhibit synaptic transmission by increasing synaptic membrane lateral pressure thereby inhibiting phospholipid hydrolysis, membrane transduction and synaptic transmission. As a first approximation towards investigating this concept, we hypothesized that anesthetics modulate the rate of phospholipase C hydrolysis of a lipid monolayer through its effects on surface pressure. The relationship between the hydrolysis rate of a monolayer of dipalmitoylphosphatidylcholine [14C-choline] (DPPC) by phospholipase C (Plase C) and monolayer surface pressure (SP) as altered by either halothane, isoflurane, or by physical compression at 37 degrees C was studied. The decline in surface 14C-activity as the [14C]choline diffuses into the Krebs-Ringer bicarbonate buffer aqueous subphase is estimated as the rate of DPPC hydrolysis measured by the initial slope method. DPPC hydrolysis was about 300 cpm/min and constant between SP of 0 to 20 dynes/cm. Higher SP between 25 and 30 dyne/cm, whether induced by halothane, isoflurane or physical compression, increased the rate of hydrolysis by 5-fold to a peak rate of about 1600 cpm/min at 25-30 dynes/cm. At a SP above 32 dynes/cm, DPPC hydrolysis abruptly ceased. We conclude that anesthetics can reversibly inhibit synaptic transmission through their effects on synaptic membrane lateral pressure. We also speculate that membrane lateral pressure may be a highly sensitive means of controlling membrane function through alteration in membrane lipid composition, membrane enzyme activity, receptor affinity and ion channel permeability.
Goodman
D M
DM
Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, School of Medicine, PA 15261, USA.
Nemoto
E M
EM
Evans
R W
RW
Winter
P M
PM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D006868:Hydrolysis; D007530:Isoflurane / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011312:Pressure; D013499:Surface Properties / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D008563:Membrane Lipids; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; D007530:Isoflurane; D010738:Type C Phospholipases; D006221:Halothane