H2 Receptor

The H2 histamine receptor is primarily responsible for gastric acid secretion and cardiac effects of Histamine. It’s a G-protein coupled receptor (Gs) found on gastric parietal cells, cardiac myocytes, smooth muscle, and some immune cells.

Activation Effects

• Gastric acid secretion (heartburn, reflux)
• Increased heart rate (positive chronotropic effect)
• Increased cardiac contractility (positive inotropic effect)
• Immune modulation (affects T cell and dendritic cell function)

Blocked By

H2 Antihistamines — famotidine (most commonly used in MCAS), cimetidine. Blocking H2 receptors reduces acid secretion and blunts the cardiac effects of histamine.

Why H1 + H2 Together

H1 and H2 receptors have different tissue distributions and different downstream effects. Blocking both covers a broader range of histamine-mediated symptoms than either alone. This is why dual antihistamine therapy is standard in MCAS management.