Systemic administration of kainate, a glutamate receptor agonist, caused neuronal death in the CA1 and CA3 fields of the rat hippocampus. In the areas of cell loss, reactive astrocytes increased their expression of an astrocyte-specific protein, glial fibrillary acidic protein (GFAP). AP-1 DNA binding activity and the expression of a 35 kDa fos-related antigen (fra) remained elevated in the rat hippocampus for at least 2 weeks after a single systemic injection of kainate, which correlated with changes in gene expression during reactive gliosis. Immunoreactivity for fras was detected in the nuclei of neurons in the dentate gyrus, but relatively few cells in CA1 and CA3 were immunoreactive 1 week after kainate treatment. However, elevated AP-1 DNA binding activity was observed in the CA1 and CA3 regions as well as in the dentate gyrus, suggesting that proteins other than the fras were involved in the astrocytic AP-1 complex. The AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promoter region of the GFAP gene, suggesting that GFAP is a potential target gene. Thus, a single systemic injection of kainate causes long-term activation of AP-1 DNA binding activity in the rat hippocampus and may be important for long-term changes in gene expression in hippocampal cells.

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The effect of dopamine (DA) on the binding of [3H]phorbol 12,13-dibutyrate ([3H]PdBu) in cultured rat striatal cells was examined. DA maximally increased specific [3H]PdBu binding by 70 +/- 10%, an increase comparable to that observed with norepinephrine (NE). This finding suggests that DA activates protein kinase C in cultured striatal cells, because increases in [3H]PdBu binding reflect translocation of protein kinase C. Half-maximal stimulation was observed with 10(-6) M DA. The peak response was observed at 2-3 min after addition of 10(-4) M DA, but [3H]PdBu binding was still increased above basal at 30 min. DA was not acting via an adrenergic receptor. Prazosin (10(-6) M) blocked the response to NE, suggesting mediation by an alpha 1-adrenergic receptor, but had little effect on the response to DA. Conversely, the D1 receptor antagonist SCH-23390 (10(-6) M) blocked the response to DA, but only partially inhibited the response to NE. Morphine (10(-6) M) inhibited the response to DA by 46 +/- 14%, but did not affect significantly the response to NE. The DA effect on [3H]PdBu binding is apparently independent of the increase in cyclic AMP seen on D1 receptor activation. Forskolin, apomorphine, and the D1 agonist SKF-38393 all increased cyclic AMP in striatal cells, but were less effective than DA in stimulating [3H]PdBu binding. The D2 agonist quinpirole was ineffective in stimulating either cyclic AMP or [3H]PdBu binding.