The effect of local anaesthetics on the thermal sensitivity of HTC cells.
Local anaesthetics caused death of HTC cells, and the order of toxicity (dibucaine > tetracaine > procaine) correlated with their oil:water partition coefficients. Cytotoxic effects of hyperthermia were enhanced by subtoxic levels of anaesthetics and again, their potency was related to the oil:water partition coefficients. DPH fluidity in plasma membranes at 37 degrees C was increased by dibucaine and tetracaine but not by procaine up to 5mM. At 43 degrees C, plasma membrane fluidity was increased by dibucaine but not by tetracaine or procaine. The results suggest that fluidisation of the hydrophobic core of the membrane may contribute to anaesthetic potentiation of heat cell death.
Kingston
C A
CA
Department of Biological Sciences, University of Durham, U.K.
Ladha
S
S
Manning
R
R
Bowler
K
K
D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D006528:Carcinoma, Hepatocellular; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003992:Dibucaine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D007700:Kinetics; D008113:Liver Neoplasms; D008560:Membrane Fluidity / Q000187:drug effects; D011343:Procaine / Q000633:toxicity; D013748:Tetracaine / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000779:Anesthetics, Local; D013748:Tetracaine; D011343:Procaine; D003992:Dibucaine