Histamine receptors activate MAPK signalling in rat hippocampus.

Histamine acts on three types of receptor, H1, associated with increased phosphoinositide turnover, H2 and H3, coupled positively and negatively to adenylil cyclase pathways, respectively. Recent report indicates that in transfected COS-7 cells the H3 receptor is associated to MAPK signaling pathways [1]. Here we investigated the effects of histamine receptor activation on MAPK phosphorilation in rat hippocampal slices. Fourhundred-μ slices were incubated in Kreb’s solution for 5 min with histamine, methylhistaprodyfen, an H1 agonist, amthamine, an H2 agonists, R-alphamethylhistamine or immepip, both H3 agonists. After overnight fixation, the slices were cut into 40-μ sections with a vibratome. Activation of p42-p44 MAPK was visualized by immunohistochemistry coupled to DAB staining using a polyclonal antibody against the phosphorylated enzyme form (antiphospho- Thr202-Tyr204). Histamine (1 and 0.1 μM), R-alpha-methylhistamine (0.1 μM), immepip (0.01 μM) and amthamine (0.1 μM) increased significantly phospho-p42/p44 MAPK (positive cell bodies) in CA3, but not in CA1, compared to control (n = 3-6, ANOVA and Newman-Keuls’s test). Methylhistaprodyfen (1 μM) had no significant effect. These results were confirmed by immunoblots of phospho-p42-p44 MAPK. Evidence indicates that MAPK regulation is necessary for memory consolidation and neuronal plasticity. This study suggests that histamine is involved in the events underlying these processes. [1]Drutel G et al (2001) Mol Pharmacol 59:1-8.