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 apparent dissociation constant (Kd) was 10.4 nM and the binding capacity (Bmax) of 262 fmol/mg protein. 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 histamine-induced Ca++ signals but pertussis toxin (IAP) and organic 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.
Department of Pharmacology II, Faculty of Medicine, Osaka University, Japan.
H
H
Fukui
N
N
Inagaki
S
S
Ito
A
A
Kubo
H
H
Kondoh
A
A
Yamatodani
H
H
Wada
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D000242:Cyclic AMP / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D007295:Inositol Phosphates; D011969:Receptors, Histamine H1; D006632:Histamine; D000242:Cyclic AMP; D011738:Pyrilamine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium