||The histamine H2-receptor (H2R) belongs to the superfamily of seven transmembrane domain (7TM), G-protein-coupled receptors (GPCRs). The endogenous agonist for the H2R is histamine which is both neurotransmitter and autacoid.The H2Rcouples to Gs-proteinsto mediate adenylate cyclase (AC) activation. In some systems, the H2R also couples to Gq-proteins and phospholipase C. Among the many responses mediated by the H2R are gastric acid secretion, smooth muscle relaxation, positive ionotropic and chronotropic effects on heart muscle, and inhibition of leukocyte function. The guinea pig H2R (gp H2R) was prepared from Sf9 cells infected with gp H2R -encoding baculovirus. In this system, gp H2R couples to the Gs-like G-proteins of the insect cells to mediate AC activation. gp H2R contains a N-terminal FLAG-tag and a Cterminal hexahistidine (His6)-tag for immunological detection, to allow purification, and to provide additional protection against proteolysis.