Histamine H₁-receptors on astrocytes in primary cultures: A possible target for histaminergic neurones

The characteristics of histamine H₁-receptors expressed on astrocytes from the cerebral cortex of new born rats were analysed by the [³H]-mepyramine binding assay. The appartent dissociatiokn constant (Kd) was 10.4 nM and the binding capacity (Bmax) was 262 fmol/mg proteinl. H₁-antagonists inhibited the [³H]mepyramine bindings and the isomers of chlorpheniramine showed a stereoselectivity for the inhibition of the bindings. Two distinct populations of cultured astrocytes, type-1 and type-2 astrocytes, were enriched and histamine-induced accumulations of inositol phosphates (IP) and cyclic AMP and histamine-evoked Ca⁺⁺ signals were examined. Histamine stimulated the accumulation of IP in type-2 astrocytes, but not in type-1 astrocytes. The accumulation of cyclic AMP induced by histamine was observed in type-1 astrocytes, although not in type-2 astrocytes. Histamine-induced Ca⁺⁺ signals were observed in 17.2% of type-1 astrocytes and in 72.9% of type-2 astrocytes. Histamine-induced Ca⁺⁺ signals in type-2 astrocytes were antagonized by H₁-antagonists, but not by H₂- antagonists. Histamine-induced Ca⁺⁺ signals were classified into 4 patterns, ie. transient, oscillatory, sustained and biphasic. When extracellular Ca⁺⁺ was omitted or La⁺⁺⁺ was added to the extracellular medium, sustained phase of Ca⁺⁺ signal disappeared and transient and oscillatory patterns were only observed. Phorbol ester inhibited histamineinduced Ca⁺⁺ signals but pertussis toxin (IAP) and orgnanic voltage dependent CA⁺⁺ channel blockers had no effect. Histamine-induced Ca⁺⁺ elevation appeared initially in processes and then Ca⁺⁺ wave propagated to the cell soma. Ca⁺⁺ elevation was observed only in the processes in some cells.