Abstract
The histamine H-4 receptor (H4R) is a classic pertussis toxin-sensitive G(i) protein-coupled receptor that mediates increases in intracellular calcium concentration ([Ca2+](i)). The presence of H4R in human eosinophils has been rigorously documented by several independent groups. It has also been suggested that H4R is expressed in human monocytes, but this suggestion hinges in part on H4R ...
Abstract
The histamine H-4 receptor (H4R) is a classic pertussis toxin-sensitive G(i) protein-coupled receptor that mediates increases in intracellular calcium concentration ([Ca2+](i)). The presence of H4R in human eosinophils has been rigorously documented by several independent groups. It has also been suggested that H4R is expressed in human monocytes, but this suggestion hinges in part on H4R antibodies with questionable specificity. This situation prompted us to reinvestigate H4R expression in human monocytes. As positive control, we studied human embryonic kidney 293T cells stably expressing the human H4R (hH(4)R). In these cells, histamine (HA) and the H4R agonist UR-PI376 (2-cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine) induced pertussis toxin-sensitive [Ca2+](i) increases. However, in quantitative real-time polymerase chain reaction studies we failed to detect hH(4)R mRNA in human monocytes and U937 promonocytes. In human monocytes, ATP and N-formyl-L-methionyl-L-leucyl-L-phenylalanine increased [Ca2+](i), but HA, UR-PI376, and 5-methylhistamine (a dual H4R/H-2 receptor agonist) did not. In U937 promonocytes and differentiated U937 cells, HA increased [Ca2+](i), but this increase was mediated via HA H-1 receptor. In conclusion, there is no evidence for the presence of H4R in human monocytes.
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