Lithium blocks a phosphoinositide-mediated cholinergic response in hippocampal slices.
The effects of lithium on inositol phosphate metabolism may account for the therapeutic actions of lithium in affective disorder. Muscarinic stimulation of the phosphoinositide system blocks synaptic inhibitory actions of adenosine in the hippocampal slice. At therapeutic concentrations, lithium diminished this muscarinic response, whereas rubidium, which does not affect phosphoinositide metabolism, had no effect. A dampening of phosphoinositide-mediated neurotransmission may explain the normalizing effects of lithium in treating both mania and depression.
Worley
P F
PF
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Heller
W A
WA
Snyder
S H
SH
Baraban
J M
JM
D000241:Adenosine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D007295:Inositol Phosphates; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; C008874:phorbol-12,13-diacetate; D010095:Oxotremorine; C042743:oxotremorine M; D002217:Carbachol; D008094:Lithium; D011493:Protein Kinase C; D000241:Adenosine