The ability of lithium to interfere with phosphoinositide metabolism in rat cerebral cortex slices has been examined by monitoring the accumulation of CMP-phosphatidate (CMP-PtdOH) and the reduction in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 levels. A small accumulation of [14C]CMP-PtdOH was seen in slices prelabelled with [14C]cytidine and stimulated with carbachol (1 mM) or Li+ (1 mM). However, simultaneous addition of both agents for 30 min produced a 22-fold accumulation, with Li+ producing a half-maximal effect at a concentration of 0.61 +/- 0.19 mM. Kinetic studies revealed that the effects of carbachol and Li+ on CMP-PtdOH accumulation occurred with no initial lag apparent under these conditions and that preincubation with myo-inositol (10 or 30 mM) dramatically attenuated CMP-PtdOH accumulation. myo-Inositol could also attenuate the rate of accumulation of CMP-PtdOH when added 20 min after carbachol and Li+; these effects were not observed when equimolar concentrations of scyllo-inositol were added. Use of specific radioreceptor assays allowed the mass accumulations of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 to be monitored. Following a lag of 5-10 min, Li+ resulted in a marked reduction in the accumulation of both inositol polyphosphates resulting from muscarinic-cholinergic stimulation. Preincubation of cerebral cortex slices with myo- (but not scyllo-) inositol delayed, but did not prevent, the reduction in the accumulation of Ins(1,4,5)P3 or Ins(1,3,4,5)P4. The results suggest that cerebral cortex, at least in vitro, is very sensitive to myo-inositol depletion under conditions of muscarinic receptor stimulation. The relationship of such depletion to the generation of inositol polyphosphate second messengers is discussed.
Skip Nav Destination
Article navigation
May 1990
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkAdvertising
Research Article|
May 01 1990
Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices
E D Kennedy;
E D Kennedy
*Department of Pharmacology and Therapeutics, University of Leicester, P.O. Box 138, Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
R A J Challiss;
R A J Challiss
*Department of Pharmacology and Therapeutics, University of Leicester, P.O. Box 138, Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
C I Ragan;
C I Ragan
†Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, U.K.
Search for other works by this author on:
S R Nahorski
S R Nahorski
*Department of Pharmacology and Therapeutics, University of Leicester, P.O. Box 138, Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
Biochem J (1990) 267 (3): 781–786.
Citation
E D Kennedy, R A J Challiss, C I Ragan, S R Nahorski; Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices. Biochem J 1 May 1990; 267 (3): 781–786. doi: https://doi.org/10.1042/bj2670781
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.