DIFFERENCES IN THE STIMULATION OF THE PHOSPHOINOSITIDE CYCLE BY AMINENEUROTRANSMITTERS IN CULTURED RAT FOREBRAIN NEURONS AND ASTROCYTES

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.