| Description : |
The histamine H1-receptor (H1R) belongs to the superfamily of seven transmembrane-domain (7TM), G-protein-coupled receptors (GPCRs). The endogenous agonist for the H1R is histamine which is both neurotransmitter and autacoid. The H1R couples to Gq-proteins to activate phospholipase C. Numerous agonists and antagonists are known. H1R agonists are divided into three classes, i.e. small agonists derived from histamine, histamine derivatives with bulkier aromatic substituents at position 2 of the imidazole ring and histaprofidens. H1R antagonists are commonly divided into sedating (first-generation) and nonsedating (second-generation) antagonists. Today, especially the second-generation H1R antagonists are of great importance for the treatment of allergic diseases. Guanidines derived from arpromidine are dual H2R agonists/ H1R antagonists. Small H1R agonists exhibit similar effects at human H1R and guinea pig H1R (gp H1R), whereas bulkier 2-phenylhistamines and histaprodifens are up to 10 fold more potent at gp H1R than at h H1R. Several first-generation H1R antagonists are 2 fold, and arpromidine-type H1R antagonists up to 10-fold more potent at gp H1R than at h H1R. Gp H1R was prepared from Sf9 cells infected with gp H1R encoding baculovirus. Gp H1R contains a N-terminal FLAG-tag and a C terminal hexahistidine (His6)-tag for immunological detection, to allow purification, and to provide additional protection against proteolysis. |
