Mixed actions of TMB-8 as a Ca2+ antagonist in cultured mouse cortical neurones.
The action of TMB-8 [8-N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate] on glutamate (Glu)- and 55 mM KCl (K+)-induced increases in intracellular free calcium levels ([Ca2+]i) was studied in cultured mouse cerebral cortical neurones. Glu-induced responses were mediated by two mechanisms, one independent of and the other dependent on extracellular Ca2+, both being inhibited by TMB-8 in a dose-dependent manner. TMB-8 had no effect on [3H]dizocilpine binding kinetics in cortical membrane preparations. The transient and sustained phases of K(+)-induced increases in [Ca2+]i were also inhibited by TMB-8 in a dose-dependent manner. The Ca2+ channel antagonist, verapamil, blocked K(+)-induced responses but had no effect on Glu-induced responses. Although TMB-8 displays multiple effects, its action at voltage-gated Ca2+ channels does not appear to contribute significantly to its inhibition of the Glu-induced increase in [Ca2+]i.
Griffiths
R
R
Division of Cell and Molecular Biology, School of Biological and Medical Sciences, University of St Andrews, Fife, Scotland, UK.
Grieve
A
A
Frandsen
A
A
Schousboe
A
A
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002451:Cell Compartmentation; D002540:Cerebral Cortex / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; D014700:Verapamil; D002118:Calcium