INVESTIGADORES
PATTERSON Sean Ingram
artículos
Título:
Neural function: metabolism and actions of inositol metabolites in mammalian brain
Autor/es:
M.R. HANLEY; T.R. JACKSON; M. VALLEJO; S.I. PATTERSON; O.THASTRUP; S. LIGHTMAN; J. ROGERS; G. HENDERSON; A. PINI
Revista:
PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON. SERIES B: BIOLOGICAL SCIENCES.
Referencias:
Año: 1988 vol. 320 p. 381 - 398
ISSN:
0962-8452
Resumen:
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.