Receptors regulating acid secretion

Histamine stimulation of gastric acid secretion has for a long time been known to be mediated by an H2-type receptor located on the parietal cell surface, but the biochemical nature of this receptor has only very recently been elucidated. It is a 70-kDa glycoprotein showing structural analogies with the beta 2-adrenergic receptor and the other seven membrane-spanning domains/G protein-coupled receptors. It activates adenylated cyclase through a cholera toxin-sensitive, pertussis toxin-insensitive, guanosine 5'-triphosphatase-binding regulatory Gs protein. The cAMP thereby produced is believed to play a crucial role in the opening of the Cl- channel associated with the (H+,K+)-ATPase in the secretory membrane. However, other sites of action are likely to be involved, since several histamine- or cAMP-dependent phosphoproteins have been detected in the parietal cell. In addition to its action on cAMP production, histamine was found to produce a transient increase in the intracellular Ca2+ concentration, but this effect remains unexplained. On the other hand, the intervention of an H3-type histamine receptor in the regulation of gastric acid secretion has recently been documented, but the cellular location of this new receptor has not been yet investigated.