Biochemical pharmacology

Analysis of the histamine H2-receptor in human monocytes.

PMID 25199456


Histamine receptors are G-protein-coupled receptors (GPCRs). Canonically, the histamine H2-receptor (H2R) couples to Gs-proteins and activates adenylyl cyclases (ACs) with subsequent adenosine-3',5'-cyclic monophosphate (cAMP) generation. Recently, the classic two-state model describing GPCR activation has been extended to a multiple-state model implying that any ligand stabilizes a ligand-specific receptor conformation, also referred to as functional selectivity. In our present study we pharmacologically characterized the H2R in human monocytes. We found dissociations in the effects of histamine (HA) and H2R agonists on cAMP accumulation and inhibition of formyl peptide-induced production of reactive oxygen species (ROS). In addition, we excluded participation of protein kinase A (PKA) in HA-induced ROS inhibition. Comparison of the potencies and efficacies of H2R agonists in monocytes, neutrophils and eosinophils unmasked cell type-specific pharmacological profiles of individual ligands. Taken together, our data extend the concept of functional selectivity to the H2R in human monocytes and demonstrate striking cell-type specificity in the pharmacological profile of the H2R.