Histamine H1-receptors mediate phosphoinositide hydrolysis in astrocyte-enriched primary cultures.
Astrocyte-enriched primary cultures of newborn rat brain hemispheres, prelabeled with [3H]inositol, accumulated [3H]inositol phosphate but not [3H]inositol bis- and tris-phosphate, after exposure to histamine for 60 min in the presence of 10 mM LiCl. The response to histamine was not a function of contaminating meningeal fibroblasts since no accumulation of [3H]inositol phosphate was elicited by histamine in meningeal cultures. The stimulation of phosphoinositide hydrolysis by histamine in astrocytes was dose-dependent (EC50 = 1.7 microM, maximal effect = 345% over basal levels) and was mimicked by several H1-receptor agonists. The use of selective receptor antagonists confirmed that the histamine response was the result of activation of H1-receptors. The histamine-induced [3H]inositol phosphate accumulation was completely abolished by omission of Ca2+ from the incubation medium. Astrocyte membranes specifically bound the radiolabeled H1-antagonist, [3H]mepyramine with an affinity (Kd = 5.9 nM) and a density of binding sites (Bmax = 113 fmol/mg protein) similar to rat brain. These results demonstrate the presence of functional histamine H1-receptors in rat brain astrocytes and suggest a role for histamine as a neuromodulator of astrocyte function.
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D006634:Histamine H1 Antagonists; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; C002647:inositol 1-phosphate; D006632:Histamine; D011738:Pyrilamine; D002118:Calcium