||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 H2R couples to Gs-proteins to 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 rat H2R was prepared from Sf9 cells infected with rat H2R-encodingbaculovirus. In this system, the rat H2R couples to the Gs-like G-proteins of the insect cells to mediate AC activation.