Activation of histamine H1-receptor enhances neurotrophic factor secretion from cultured astrocytes

Objective:Histamine stimulates nerve growth factor (NGF) secretion from cultured astrocytes. Histamine H-1-receptor antagonists completely block its effect. In the present study, we determined the involvement of histamine-receptor subtypes in this process. Materials and methods:Radioligand-binding assay was used to establish the presence of histamine H-1- and H-2-receptors on new-born rat cortical astrocytes in primary culture. Histamine H-1-, H-2- and H-3/H-4-receptor ligands, and highly selective protein kinase C (PKC) inhibitor were used to influence NGF secretion from cultured astrocytes. NGF, released into the culture medium, was measured by NGF-ELISA. Results:Histamine H-1-receptor agonists (histamine, selected histaprodifens) increased the secretion of NGF from cultured astrocytes in a concentration-dependent manner. H-1-receptor antagonists/inverse agonists (mepyramine, triprolidine) and PKC inhibitor completely blocked the effect of histamine. Histamine H-2- and H-3-receptor agonists did not enhance NGF secretion significantly. In addition, H-2- and H-3/H-4-receptor antagonists did not diminish histamine-stimulated NGF release. Conclusions:Our results indicate that histamine H-1-receptor and PKC are involved in the signal transduction pathway, responsible for histamine-stimulated NGF secretion from cultured astrocytes.