21.4 : 消化性潰瘍疾患の酸分泌抑制薬：ヒスタミン H2 受容体拮抗薬

Histamine H₂ receptors are G protein-coupled receptors located on the basolateral membrane of parietal cells.

Histamine released from ECL cells binds to these receptors and initiates the cyclic AMP pathway.

Adenylyl cyclase converts ATP to cAMP, increasing intracellular cAMP levels and activating PKA.

Activated PKA stimulates the proton pump to secrete H⁺ in exchange for K⁺.

H₂ receptor antagonists compete with histamines for H₂ receptors, blocking the binding of histamine to the receptors and suppressing gastric acid production.

Additionally, in the presence of these blockers, the direct stimulation of parietal cells by acetylcholine or gastrin diminishes. This reduces gastrin- or acetylcholine-stimulated acid production.

Cimetidine, ranitidine, famotidine, and nizatidine are four different H₂ receptor antagonists.

These blockers effectively suppress gastric acid secretion during sleep, healing ulcers. The drugs are metabolized in the liver and cleared through the kidneys. So, lower doses are advised for the elderly or those with poor renal function.