Veratrine-stimulated phosphoinositide breakdown as an assay for local anesthetic actions at Na+ channels.
The blockade of veratrine-stimulated phosphoinositide breakdown in rat cerebral cortical miniprisms as a model of local anesthetic actions on voltage-dependent sodium channels was assessed. Veratrine stimulated phosphoinositide breakdown with an EC50 value of 5 microM. The stimulation produced by 20 microM veratrine was blocked completely by (+)-bupivacaine (IC50 7.6 microM [mean of three separate experimental series]), (-)-bupivacaine (IC50 7.3 microM), lidocaine (IC50 34 microM), etidocaine (IC50 3.4 microM), tetracaine (IC50 approximately 2 microM), and prilocaine (IC50 110 microM). Phosphoinositide breakdown responses to ouabain (100-1000 microM) and K+ (50 mM) were only partially blocked by (+)-bupivacaine, and the responses to monensin (100 and 1000 microM) and noradrenaline (30 microM) were not blocked at all by this drug. Nifedipine produced no significant effects on the phosphoinositide response to 10 microM veratrine. It is concluded that in pulse label experiments using rat cerebral cortical miniprisms, local anesthetics in general, and (+)-bupivacaine in particular, block the phosphoinositide response to veratrine with a high degree of specificity. This system may be useful as a relatively simple and quantitative assay for drug effects on Na(+)-channels.
Tiger
G
G
Department of Pharmacology, Umeå University, Sweden.
Lundin
D
D
Fowler
C J
CJ
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D004347:Drug Interactions; D006868:Hydrolysis; D008297:Male; D008985:Monensin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D015222:Sodium Channels / Q000187:drug effects*; D013268:Stimulation, Chemical; D014702:Veratrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D000779:Anesthetics, Local; D010716:Phosphatidylinositols; D015222:Sodium Channels; D010042:Ouabain; D008985:Monensin; D014702:Veratrine; D011188:Potassium; D002045:Bupivacaine