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.


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.
Lipnik-Stangelj
M
M
Department of Pharmacology, Faculty of Medicine, Korytkova 2, 1000 Ljubljana, Slovenia. metoda.lipnik-stangelj@mf.uni-lj.si
Carman-Krzan
M
M
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism; D015398:Signal Transduction
D003470:Culture Media; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D009414:Nerve Growth Factors; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D020932:Nerve Growth Factor; D011493:Protein Kinase C; C070515:bisindolylmaleimide I