Session 2: Receptors Regulating Acid Secretion

Abstract

Lewin MJM, Bado A. Receptors regulating acid secretion. Scand J Gastroenterol 1991, 26(suppl 180), 53–57

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 β₂-adrenergic receptor and the other seven membrane-spanning domains/G protein-coupled receptors. It activates adenylate cyclase through a cholera toxin-sensitive, pertussis toxin-insensitive, guano-sine 5″-triphosphatase-binding regulatory Gs protein. The cAMP thereby produced is believed to play a crucial role in the opening of the CI⁻ 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.

Key Words:

• cAMP
• Ca²⁺
• gastric acid secretion
• histamine
• parietal cell
• protein phosphorylation
• H₂ receptor
• H₃ receptor