Potentiation by a sodium channel activator of effects of lithium ion on cyclic AMP, cyclic GMP and inositol phosphates.
The effects of the lithium ion (Li+) on receptor-mediated synthesis of second messengers were determined, when cellular sodium channels were quiescent or excited, using the murine neuroblastoma clone (N1E-115). In this clone, lithium inhibited the receptor-mediated synthesis of cyclic AMP and cyclic GMP and it also increased the accumulation of inositol phosphates by a receptor-mediated process. When veratridine (20 microM) excited the sodium channel, the effects of lithium were potentiated. However, tetrodotoxin, a sodium channel blocker, completely prevented this potentiation. These results suggest that when neurons are depolarizing actively and intraneuronal levels of lithium increase by entry through the sodium channel, lithium has a more potent intracellular effect. As a result, lithium would have more potent and selective effects in those pathologically-active neurons underlying manic-depressive disorder.
Kanba
S
S
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Yagi
G
G
Nakaki
T
T
Kato
R
R
Richelson
E
E
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000096:biosynthesis* / Q000378:metabolism; D007477:Ions; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects; D015222:Sodium Channels / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D007295:Inositol Phosphates; D007477:Ions; D011976:Receptors, Muscarinic; D015222:Sodium Channels; D014701:Veratridine; D008094:Lithium; D000242:Cyclic AMP; D006152:Cyclic GMP