Potassium ions potentiate the muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex slices: A comparison of neonatal and adult rats

1990 ◽  
Vol 15 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Walter Balduini ◽  
Lucio G. Costa ◽  
Sheldon D. Murphy
Keyword(s):  
Cerebral Cortex ◽  
Muscarinic Receptor ◽  
Potassium Ions ◽  
Phosphoinositide Metabolism ◽  
Adult Rats ◽  
Cortex Slices

scholarly journals Rapid accumulation and sustained turnover of inositol phosphates in cerebral-cortex slices after muscarinic-receptor stimulation

1989 ◽  
Vol 260 (1) ◽  
pp. 237-241 ◽  
Author(s):  
I H Batty ◽  
S R Nahorski
Keyword(s):  
Cerebral Cortex ◽  
Muscarinic Receptor ◽  
Metabolic Flux ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Receptor Activation ◽  
Inositol Polyphosphate ◽  
Receptor Stimulation ◽  
Cortex Slices ◽  
Rapid Kinetics

The rapid kinetics of [3H]inositol phosphate accumulation and turnover were examined in rat cerebral-cortex slices after muscarinic-receptor stimulation. Markedly increased [3H]inositol polyphosphate concentrations were observed to precede significant stimulated accumulation of [3H]inositol monophosphate. New steady-state accumulations of several 3H-labelled products were achieved after 5-10 min of continued agonist stimulation, but were rapidly and effectively reversed by subsequent receptor blockade. The results show that muscarinic-receptor activation involves phosphoinositidase C-catalysed hydrolysis initially of polyphosphoinositides rather than of phosphatidylinositol. Furthermore, prolonged carbachol stimulation is shown not to cause receptor desensitization, but to allow persistent hydrolysis of [3H]phosphatidylinositol bisphosphate and permit sustained metabolic flux through the inositol tris-/tetrakis-phosphate pathway.

scholarly journals Lithium inhibits muscarinic-receptor-stimulated inositol tetrakisphosphate accumulation in rat cerebral cortex

1987 ◽  
Vol 247 (3) ◽  
pp. 797-800 ◽  
Author(s):  
I Batty ◽  
S R Nahorski
Keyword(s):  
Cerebral Cortex ◽  
Steady State ◽  
Inhibitory Action ◽  
Rat Cerebral Cortex ◽  
Phosphoinositide Metabolism ◽  
Muscarinic Agonist ◽  
Complex Action ◽  
Inositol 1,4,5 Trisphosphate ◽  
Inositol Tetrakisphosphate ◽  
Cortex Slices

The effects of Li+ on carbachol-stimulated phosphoinositide metabolism were examined in rat cerebral-cortex slices labelled with myo-[2-3H]inositol. The muscarinic agonist carbachol evoked an enhanced steady-state accumulation of [3H]inositol monophosphate ([3H]InsP1), [3H]inositol bisphosphate ([3H]InsP2), [3H]inositol 1,3,4-trisphosphate ([3H]Ins(1,3,4)P3), [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) and [3H]inositol tetrakisphosphate ([3H]InsP4). Li+ (5 mM), after a 10 min lag, severely attenuated carbachol-stimulated [3H]InsP4 accumulation while simultaneously potentiating accumulation of both [3H]InsP1 and [3H]InsP2 and, at least initially, of [3H]Ins(1,3,4)P3. These data are consistent with inhibition of inositol mono-, bis- and 1,3,4-tris-phosphate phosphatases to different degrees by Li+ in brain, but are not considered to be completely accounted for in this way. Potential direct and indirect mechanisms of the inhibitory action of Li+ on [3H]InsP4 accumulation are considered. The present results stress the complex action of Li+ on cerebral inositol metabolism and indicate that more complex mechanisms than are yet evident may regulate this process.

scholarly journals Differences between muscarinic-receptor- and Ca2+-induced inositol polyphosphate isomer accumulation in rat cerebral-cortex slices

1990 ◽  
Vol 267 (3) ◽  
pp. 835-838 ◽  
Author(s):  
J G Baird ◽  
S R Nahorski
Keyword(s):  
Cerebral Cortex ◽  
Muscarinic Receptor ◽  
Degradation Products ◽  
The Other ◽  
Rat Cerebral Cortex ◽  
Inositol Polyphosphate ◽  
Receptor Stimulation ◽  
Other Hand ◽  
Cortex Slices ◽  
Polyphosphate Metabolism

Muscarinic-receptor stimulation or depolarization by elevated K+ leads to increased accumulation of [3H]Ins(1,4,5)P3, [3H]Ins(1,3,4,5)P4 and several degradation products of these polyphosphates separated by h.p.l.c. On the other hand, agents such as ionomycin and maitotoxin, which increase intracellular Ca2+ directly, produce a small accumulation of [3H]Ins(1,4,5)P3 and markedly increase [3H]Ins(1,4)P2, but [3H]Ins(1,3,4,5)P4, [3H]Ins(1,3,4)P3 and [3H]Ins(1,3)P2 are virtually unaffected. Ca2(+)-dependent [3H]inositol polyphosphate metabolism may involve different pools of lipids and/or phosphoinositidases.

scholarly journals Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices

1990 ◽  
Vol 267 (3) ◽  
pp. 781-786 ◽  
Author(s):  
E D Kennedy ◽  
R A J Challiss ◽  
C I Ragan ◽  
S R Nahorski
Keyword(s):  
Cerebral Cortex ◽  
Second Messengers ◽  
Kinetic Studies ◽  
Phosphoinositide Metabolism ◽  
Maximal Effect ◽  
Inositol Polyphosphate ◽  
Inositol Polyphosphates ◽  
Cortex Slices ◽  
Relationship Of

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.

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