Effects of lithium and desimipramine on second messenger responses in rat hippocampus: relation to G protein effects.
The effects of chronic administration of lithium, short-term administration of lithium, chronic administration of DMI and a combination of short-term administration of lithium and chronic administration of DMI on second messenger responses were studied in the hippocampus of the rat. Lithium reduced the ability of carbachol to inhibit forskolin-stimulated activity of adenylate cyclase in hippocampal membranes but had no effect on carbachol-stimulated formation of inositol phosphate in hippocampal slices. Lithium, however, reduced the degree of stimulation of formation of inositol phosphate, induced by noradrenaline. Desimipramine alone did not affect carbachol- or noradrenaline-mediated reactions and a combination of short-term administration of lithium and chronic administration of DMI did not potentiate the action of lithium on adenylate cyclase. Both lithium and DMI abolished the inhibition by 5-HT of carbachol-stimulated formation of inositol phosphate a 5-HT1A receptor-mediated response. It is concluded that the chronic effects of administration of lithium may be related to actions at the G protein level and that different modes of coupling of receptors to G proteins may be responsible for the variety of effects observed.
Newman
M E
ME
Yaacov Herzog Centre for Brain and Psychiatry Research, Ezrath Nashim Hospital, Jerusalem, Israel.
Shapira
B
B
Lerer
B
B
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects*
D007295:Inositol Phosphates; D005576:Colforsin; D002217:Carbachol; D008094:Lithium; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D003891:Desipramine