Beyond Digestion: Secretin as a Key Regulator of Systemic pH

Secretin is a broad activator of epithelial bicarbonate secretion and regulates local and systemic pH balance along with metabolic functions. Its receptor, widely expressed across epithelial and neuroendocrine tissues, enables coordinated responses to digestive phases, systemic alkalosis, and volume regulation. This positions secretin as a corrective hormone of the postprandial alkaline tide and a critical signaling pathway in the prevention of excessive systemic alkalosis. Its signaling intersects with the renin-angiotensin-aldosterone system, where secretin, angiotensin II, and aldosterone jointly enhance pendrin-mediated chloride reabsorption and bicarbonate secretion during states such as Cl- depletion alkalosis. Conditions with disrupted secretin signaling, most notably cystic fibrosis, demonstrate the physiological importance of secretin-dependent bicarbonate secretion in pancreatic, biliary, renal, and potentially airway epithelia. Overall, secretin emerges not only as a gastrointestinal regulator but also as a central, integrative hormone linking digestion, metabolism, local and systemic acid-base homeostasis, renal electrolyte handling, and systemic volume regulation.