Comparison of α1‐Adrenergic Receptor‐Stimulated Inositol Phosphate Formation in Primary Neuronal and Glial Cultures

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Abstract
.alpha.1-Adrenergic receptor binding sites and norepinehprine-stimulated 3H-inositol phosphate (3H-InsP) accumulation were measured in primary cultures of neurons and gila from 1-day-old rat brains. The density of .alpha.1-afrenergic receptor binding sites was .apprx. three times higher in membranes from neurons compared to glia. Although norepinehprine was slightly more potent in stimulating 3H-InsP formation in neurons than in glia, the maximal response was greater in glial cells. Norepinehprine-stimulated 3H-InsP formation remained constant for [3H]inositol prelabeling periods of 1-14 days in neurons, whereas the response increased with time in glia and was maximal after 7-10 days of prelabeling. Both the incorporation of [3H]inositol into lipid and basal levels of 3H-InsPs were lower in glial cells than in neurons, which accounted for the greater percent stimulation in glia. Pretreatment with phenoxybenzamine decreased norepinephrine-stimulated 3H-InsP formation in a dose-dependent manner in both neurons and glia by decreasing the maximal response without altering potency. HPLC separation showed that similar types of 3H-InsPs were accumulated in neurons and glial cells. These results demonstrate that .alpha.1-adrenergic receptors exist on both neurons and glial cells and activate 3H-InsP accumulation in both cell types. Although receptor density is higher in neurons than in glia, the 3H-InsP response is higher in glia. This difference does not appear to be due to different receptor reserves, but may be due to differential coupling mechanisms in the two cell types.