Effects of lithium ex vivo on the GTP-mediated inhibition of calcium-stimulated adenylate cyclase activity in rat brain.
The aim of this study was to investigate the effects of chronic lithium treatment on calcium (Ca2+)-stimulated adenylate cyclase activity in rat striatum and hippocampus, and to elucidate the effect of lithium treatment on the neurotransmitter/GTP-mediated inhibition of Ca2+-stimulated enzyme activity in the two brain areas. Lithium treatment, which gave a serum-lithium concentration of 0.9 +/- 0.16 mmol/l, enhanced Ca2+-stimulated enzyme activity in the hippocampus but reduced this activity in the striatum. Serotonin (5-HT) dose dependently reduced Ca2+-stimulated adenylate cyclase activity in the hippocampus, and chronic lithium administration reduced the ability of 1 microM 5-HT to inhibit Ca2+-stimulated enzyme activity. Furthermore, the 5-HT-induced GTP-mediated inhibition of Ca2+-stimulated adenylate cyclase activity in the hippocampus was markedly decreased by lithium. Increasing concentrations of dopamine in the striatum did not, however, affect Ca2+-stimulated adenylate cyclase activity and the inhibition of enzyme activity observed with increasing concentrations of GTP was not influenced by chronic lithium treatment. These results demonstrate that lithium ex vivo exerts dual and region-specific effects on Ca2+-stimulated adenylate cyclase in the brain. Furthermore, long-term administration of lithium could reduce the inhibitory effect of 5-HT on adenylate cyclase in the hippocampus, by influencing the inhibitory GTP-binding protein. The effects of lithium on serotonergic and dopaminergic neurotransmission could be involved in the therapeutic actions of lithium in manic-depressive illness.
Mørk
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Department of Pharmacology, University of Copenhagen, Denmark.
Geisler
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D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004789:Enzyme Activation; D006160:Guanosine Triphosphate / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006160:Guanosine Triphosphate; D008094:Lithium; D000262:Adenylyl Cyclases; D002118:Calcium