Neural function: metabolism and actions of inositol metabolites in mammalian brain
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Neural function : metabolism and actions of inositol metabolites in mammalian brain. / Hanley, M R; Jackson, T R; Vallejo, M; Patterson, S I; Thastrup, Ole; Lightman, S; Rogers, J; Henderson, G; Pini, A.
In: Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 320, No. 1199, 1988, p. 381-98.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Neural function
T2 - metabolism and actions of inositol metabolites in mammalian brain
AU - Hanley, M R
AU - Jackson, T R
AU - Vallejo, M
AU - Patterson, S I
AU - Thastrup, Ole
AU - Lightman, S
AU - Rogers, J
AU - Henderson, G
AU - Pini, A
PY - 1988
Y1 - 1988
N2 - In the nervous system, a variety of cell types respond to external stimuli through the inositol lipid signalling pathways. The stimulus-coupled sequence of intracellular events has been investigated in a homogeneous model system, the cloned mammalian neural cell line NG115-401L. The neural peptide bradykinin stimulates a rapid production of identified inositol phosphate isomers and an intracellular Ca2+ discharge followed by a persistent plasma membrane influx. The temporal sequence suggests that Ins(1,4,5)P3 or Ins(1,3,4,5)P4 or both may coordinate these events in a neuronal cell, as has been suggested in other cell types. Thapsigargin, an irritant and tumour-promoting plant product, produces calcium transients in the absence of inositol phosphate production, and may provide a new tool for investigating the interactions between inositol phosphates and changes in cellular calcium homeostasis. In the 401L line, high levels of radiolabelled InsP5 and InsP6 have been detected, which has led to the evaluation of their possible occurrence and actions in normal brain. Both InsP5 and InsP6 are produced from a radiolabelled myo-inositol precursor in intact mature brain in a region-specific manner. This suggests that both inositol polyphosphates may be end products of regionally regulated biosynthetic pathways. When microinjected into a nucleus of the brainstem, or iontophoretically applied to the dorsal horn of the spinal cord, both InsP5 and InsP6, but not Ins(1,3,4,5)P4 isomers, appear to be potent neural stimulants. These results suggest that the inositol lipid signalling pathways may generate both intracellular and extracellular signals in brain.
AB - In the nervous system, a variety of cell types respond to external stimuli through the inositol lipid signalling pathways. The stimulus-coupled sequence of intracellular events has been investigated in a homogeneous model system, the cloned mammalian neural cell line NG115-401L. The neural peptide bradykinin stimulates a rapid production of identified inositol phosphate isomers and an intracellular Ca2+ discharge followed by a persistent plasma membrane influx. The temporal sequence suggests that Ins(1,4,5)P3 or Ins(1,3,4,5)P4 or both may coordinate these events in a neuronal cell, as has been suggested in other cell types. Thapsigargin, an irritant and tumour-promoting plant product, produces calcium transients in the absence of inositol phosphate production, and may provide a new tool for investigating the interactions between inositol phosphates and changes in cellular calcium homeostasis. In the 401L line, high levels of radiolabelled InsP5 and InsP6 have been detected, which has led to the evaluation of their possible occurrence and actions in normal brain. Both InsP5 and InsP6 are produced from a radiolabelled myo-inositol precursor in intact mature brain in a region-specific manner. This suggests that both inositol polyphosphates may be end products of regionally regulated biosynthetic pathways. When microinjected into a nucleus of the brainstem, or iontophoretically applied to the dorsal horn of the spinal cord, both InsP5 and InsP6, but not Ins(1,3,4,5)P4 isomers, appear to be potent neural stimulants. These results suggest that the inositol lipid signalling pathways may generate both intracellular and extracellular signals in brain.
KW - Animals
KW - Brain
KW - Cell Line
KW - Cell Membrane
KW - Humans
KW - Inositol
KW - Inositol Phosphates
KW - Neurons
KW - Sugar Phosphates
M3 - Journal article
C2 - 2906145
VL - 320
SP - 381
EP - 398
JO - Philosophical Transactions of the Royal Society B: Biological Sciences
JF - Philosophical Transactions of the Royal Society B: Biological Sciences
SN - 0962-8436
IS - 1199
ER -
ID: 43350250