The effect of local anaesthetics on the ryanodine receptor/Ca2+ release channel of brain microsomal membranes.
The effects of various local anaesthetics (LAs) on ryanodine binding of the sheep brain ryanodine receptor were tested. Tetracaine and dibucaine inhibit the binding with half-maximal inhibition (CI50) of 0.12 mM and 0.7 mM, respectively. Lidocaine and its analog QX-314, on the other hand, stimulate the binding up to 3-fold with half-maximal stimulation occurring with about 2 mM of the drugs. Lidocaine increases both the receptor affinity for ryanodine by about 5-fold and the rate of ryanodine association with its binding site by about 6-fold. Tetracaine and lidocaine also interact with the purified brain ryanodine receptor and produce inhibitory and stimulatory effects similar to those obtained with the membrane-bound receptor. The interaction of the LAs with the brain ryanodine receptor, as well as with the skeletal muscle receptor [J. Memb. Biol. 133 (1993) 171-182], suggest that ryanodine receptor possesses intrinsic binding site(s) for LAs.
Department of Life Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
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Martin
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Ashley
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Shoshan-Barmatz
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012756:Sheep
D000779:Anesthetics, Local; D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002118:Calcium