Am. Oliva et al., DIFFERENCES IN THE STIMULATION OF THE PHOSPHOINOSITIDE CYCLE BY AMINENEUROTRANSMITTERS IN CULTURED RAT FOREBRAIN NEURONS AND ASTROCYTES, Biochemical pharmacology, 54(11), 1997, pp. 1243-1251
In this study, we compared the stimulation by carbachol (CCh), noradre
naline (NA), and histamine (HA) of phosphoinositide hydrolysis in rat
forebrain neuronal and glial cultures. When Ca2+ was omitted from the
stimulation buffer (low mu M extracellular Ca2+), amine-induced [H-3]i
nositol phosphate accumulation was reduced to a higher extent in astro
cytes (70-80% for CCh and NA and 100% for HA) than in neurones (around
50-60% for all the amines). Furthermore, guanosine 5'-[gamma-thio]tri
sphosphate (GTP[SI) stimulation of phosphoinositidase C (PIG) in membr
anes was 5-fold higher in neurones than in astrocytes. These results i
ndicate differences in the mechanism of PIC stimulation in the two cel
l types. After 30 min stimulation in the presence of 10 mM Li+, a high
er accumulation of [H-3]inositol 4-monophosphate and [H-3]inositol 1,4
-bisphosphate than of [H-3]inositol 1/3-monophosphate occurred for all
agonists in neurones, whereas the opposite was observed in astrocytes
. Moreover, in these cells stimulation for 5 min in the absence of Li produced a 2-3-fold accumulation of all metabolites of the 3-kinase p
athway of inositol 1,4,5 trisphosphate metabolism but not of those of
the 5-phosphatase pathway. Thus, regardless of the amine receptor stim
ulated, the 3-kinase route appeared to prevail in astrocytes and the 5
-phosphatase pathway in neurones. The histamine response in neurones d
iffered from that of the other agonists in that it rapidly declined. T
aken together these results indicate that the heterogeneity in amine s
timulation of the phosphoinositide cycle previously observed in brain
slices could arise to a great extent from the cellular diversity of th
is preparation and be related to the differential contribution of the
amine receptors located in neurones and astrocytes. (C) 1997 Elsevier
Science Inc.