Lithium treatment of affective disorders; effects on the cyclic AMP and inositol phospholipid signalling pathways’
dc.contributor.author | Sillence, Daniel J. | en |
dc.contributor.author | Downes, C. P. | en |
dc.date.accessioned | 2015-03-09T11:00:04Z | |
dc.date.available | 2015-03-09T11:00:04Z | |
dc.date.issued | 1992 | |
dc.description.abstract | The effects of lithium (Li+) on the adenylyl cyclase and inositol phospholipid receptor signalling pathways were compared directly in noradrenergic and carbachol stimulated rat brain cortical tissue slices. Li+ was a comparatively weak inhibitor of noradrenaline-stimulated cyclic AMP accumulation with an IC50 of approx. 20 mM. By contrast, half-maximal effects of Li+ on inositol monophosphate (InsP) accumulation in [3H]inositol labelled tissue slices occurred at about 1 mM. A similar IC50 for Li+ of about 1 mM was also obtained for noradrenaline-stimulated accumulation of CMP-phosphatidate (CMPPA), a sensitive indicator of intracellular inositol depletion, in tissue slices that had been prelabelled with [3H]cytidine. The effect of myo-inositol (inositol) depletion on the prolonged activity of phosphoinositidase C (PIC) was examined in carbachol-stimulated cortical slices using a novel mass assay for InsP. Exposure to a maximal dose of carbachol for 30 min in the presence of 5 mM Li+ caused a 10-fold increase in the level of radioactivity associated with the InsP fraction, but only a 2-fold increase in InsP mass. During prolonged incubations in the presence of both carbachol and Li+ the accumulation of InsP mass was enhanced if 30 mM inositol was included in the medium. The results are compatible with the inositol depletion hypothesis of Li+ action but do not support the concept that adenylyl cyclase or guanine nucleotide dependent proteins represent therapeutically relevant targets of this drug. | en |
dc.funder | MRC | en |
dc.identifier.citation | Sillence, D.J. and Downes, C.P. (1992) Lithium treatment of affective disorders; effects on the cyclic AMP and inositol phospholipid signalling pathways. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1138 (1), pp. 46-52 | en |
dc.identifier.doi | https://doi.org/10.1016/0925-4439(92)90150-L | |
dc.identifier.uri | http://hdl.handle.net/2086/10761 | |
dc.language.iso | en | en |
dc.peerreviewed | Yes | en |
dc.projectid | MRC PhD studentship | en |
dc.publisher | Elsevier | en |
dc.researchinstitute | Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI) | en |
dc.subject | Inositol Phosphates | en |
dc.title | Lithium treatment of affective disorders; effects on the cyclic AMP and inositol phospholipid signalling pathways’ | en |
dc.type | Article | en |
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