Effects of GTP on hormone-stimulated adenylate cyclase activity in cerebral cortex, striatum, and hippocampus from rats treated chronically with lithium.
The effects of lithium on guanosine triphosphate (GTP) stimulated adenylate cyclase activity and hormone-induced GTP activation of the enzyme have been studied in three regions of the rat brain. Chronic treatment with lithium, giving a serum lithium level of 0.71 +/- 24 mmol/L, reduced isoprenaline-induced GTP stimulation of adenylate cyclase activity in cortical membranes at concentrations of GTP up to 2 microM. No effect of lithium was observed at higher concentrations of GTP. The enzyme activity stimulated by GTP alone was unaltered by lithium ex vivo. In striatal membranes, lithium ex vivo decreased both dopamine-induced GTP activation of adenylate cyclase and GTP-stimulated adenylate cyclase activity at concentrations of GTP below 2 microM. No effects of lithium ex vivo were found in striatum at 2 microM GTP and above. In hippocampal membranes, lithium ex vivo did not influence either serotonin-induced GTP stimulation of the adenylate cyclase or GTP-stimulated enzyme activity at low levels of GTP. However, at 50 microM GTP, lithium ex vivo enhanced serotonin-stimulated enzyme activity. The present results suggest that lithium ex vivo decreases neurotransmitter activation of the cortical beta-adrenergic adenylate cyclase by influencing the mechanisms by which receptor agonists enhance the GTP stimulation of the adenylate cyclase. Furthermore, lithium ex vivo exerts a region-specific action on the brain adenylate cyclases, but in the brain regions studied, an effect of lithium on N-protein level might be of significance for the action of lithium ex vivo on neurotransmitter activation.
Mørk
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Department of Pharmacology, University of Copenhagen, Denmark.
Geisler
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D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002712:Chlorides / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007545:Isoproterenol / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013570:Synaptic Membranes / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D002712:Chlorides; D018377:Neurotransmitter Agents; D012701:Serotonin; D006160:Guanosine Triphosphate; D008094:Lithium; D018021:Lithium Chloride; D007545:Isoproterenol; D004298:Dopamine