Our results suggest that histamine stimulated neutrophil adhesion is due to H1 and H2 receptor mediated activation of PLC, NOS and GC. Increase of cAMP concentration seems to mediate an inhibitory effect on PMN adhesion to endothelial cells.
We conclude that the antibodies generated against the extra-cellular domain of the H2 receptor are specific and can be utilized to detect and quantify H2 receptor expression. Furthermore, the significant differences in H2 receptor expression in different vascular cell types might play a critical role in defining histamine induced cellular responses during physiological or pathophysiological processes.
During agonist-dependent long-term stimulation of cells, histamine receptor subtypes are frequently down-regulated. However, the mechanisms underlying the modulation of receptor expression during long-term histamine stimulation have yet to be resolved. Based on our recently reported results showing an H1-mediated down-regulation of histamine H2 receptor mRNA in endothelial cells, our aim was to characterize the mechanism controlling rapid and long-term histamine-mediated modulation of H2 receptor expression in more detail. We were able to show that the histamine-induced down-regulation of H2 receptor mRNA and cell surface expression lasting for 24 h was accompanied by augmentation of the receptor protein level in the cytoplasmatic fraction of endothelial cells for this time period. Furthermore, changes in receptor protein levels in whole-cell lysate were negligible, indicating that the rapid and prolonged modulation of cell surface H2 receptor levels by histamine was regulated solely via internalization. The role of nitric oxide (NO) as a key mediator in histamine-stimulated cell responses was underlined by subsequent studies showing the attenuation of histamine-induced H2 receptor mRNA down-regulation and protein trafficking following NO synthase isozyme inhibition.
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