Histamine H 1-receptors mediate phosphoinositide hydrolysis in astrocyte-enriched primary cultures

Abstract

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 (EC 50 = 1.7 μM, maximal effect = 345% over basal levels) and was mimicked by several H 1-receptor agonists. The use of selectiver receptor antagonists confirmed that the histamine response was the result of activation of H 1-receptors. The histamine-induced [ 3H]inositol phosphate accumulation was completely abolished by omission of Ca 2+ from the incubation medium. Astrocyte membranes specifically bound the radiolabeled H 1-antagonist, [ 3H]mepyramine with an affinity ( K d = 5.9 nM) and a density of binding sites ( B max = 113 fmol/mg protein) similar to rat brain. These results demonstrate the presence of functional histamine H 1-receptors in rat brain astrocytes and suggest a role for histamine as a neuromodulator of astrocyte function.