The use of molecular probes in the study of the action of histamine on macrophages.

The effect of histamine on the expression in vitro of C2, factor B and C3 genes in murine resident peritoneal macrophages was investigated. By measuring the levels of specific mRNA and the amount of the biosynthetically labelled gene products, we found that histamine decreases the biosynthesis of C2 and factor B. However, histamine had virtually no effect on the biosynthesis of C3 in the same cells. To clarify the mechanism of these effects, the H1 agonists (2-pyridylethylamine (PEA)and 2-methylhistamine), the H2-agonists (impromidine and 4-methyl-histamine), the H1-antagonist (chlorpheniramine) as well as the H2-antagonist (cimetidine) were also tested. We found that the inhibitory effect of histamine on C2 and factor B is produced only through H2 receptors. With the combination of histamine agonists and antagonists an inverse effect via H1- or H2-receptors was determined on the biosynthesis of C3. H1-receptor stimuli enhanced, and the stimulation of H2-receptors inhibited, C3 biosynthesis. All effects were pretranslational since the same results were obtained on mRNA and protein levels.