Lithium-induced reduction in intracellular inositol supply in cholinergically stimulated parotid gland.
The effects of lithium and cholinergic stimulation on inositol phospholipid metabolism have been assessed using rat parotid gland slices and isolated acinar cells labelled with 32Pi. Cholinergic stimulation using carbachol caused substantial breakdown of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) and enhanced labelling of phosphatidate (PA) and phosphatidylinositol (PtdIns). Lithium alone had little effect upon 32Pi incorporation, but in combination with carbachol it greatly reduced the PtdIns labelling response to the agonist. Instead the label accumulated in a lipid identified as cytidine monophosphorylphosphatidate. There was also an enhancement of the PA labelling response to carbachol. These lithium-induced alterations in agonist-stimulated phospholipid metabolism were reversed if 10-30 mM-inositol was included in the incubation medium. Despite reduced PtdIns synthesis, lithium had relatively little effect on polyphosphoinositide labelling in stimulated cells. Resynthesis of polyphosphoinositides was monitored in acinar cells that had been stimulated with carbachol and then treated with atropine to block muscarinic receptors. Treatment with lithium during the carbachol-stimulation phase reduced the rate of phosphatidylinositol 4-phosphate synthesis, but had no significant effect upon PtdInsP2. The results suggest that an active inositol phosphatase pathway is essential to maintain intracellular inositol levels, but that PtdInsP2 synthesis is not markedly reduced by a substantial fall in intracellular inositol. This implies a close control over the rates of PtdInsP2 breakdown and resynthesis during agonist stimulation.
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D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013268:Stimulation, Chemical
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D007294:Inositol; D002217:Carbachol; D008094:Lithium