title: Anesthetics modulate phospholipase C hydrolysis of monolayer phospholipids by surface pressure.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, School of Medicine, PA 15261, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Goodman
authors.forename: E M
authors.initials: EM
authors.lastname: Nemoto
authors.forename: R W
authors.initials: RW
authors.lastname: Evans
authors.forename: P M
authors.initials: PM
authors.lastname: Winter
mesh_terms: 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*
chemical_list: D018685:Anesthetics, Inhalation; D008563:Membrane Lipids; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; D007530:Isoflurane; D010738:Type C Phospholipases; D006221:Halothane