In 1902 Bayliss and Starling discovered the first peptide hormone, secretin. Secretin is released in response to food intake and the postprandial effects of secretin in the gastrointestinal system are well explained and understood. Here, its effect are well-understood: it activates pancreatic and bile duct bicarbonate secretion and inhibits gastric acid secretion. Beyond the gastrointestinal system, the secretin receptor is also expressed in the kidney, where it has been implicated in water conservation, although the mechanism remained uncertain.

We have discovered that secretin via its receptor controls renal base excretion by activation of the base secretion in beta-intercalated cells of the kidney collecting duct. Notably, secretin-release is augmented during acute metabolic alkalosis. Consequently, loss of the secretin receptor impairs the kidneys’ ability to increase renal base excretion and compensate an acutely imposed metabolic alkalosis.

Additionally, we have uncovered that secretin also strongly modulates the glomerular filtration rate by selective vasodilation of the vas efferens, thereby controls urine production. Both effects – decreased renal acid excretion and decreased urine production – can be viewed as beneficial in the postprandial state by normalizing the postprandial blood alkalinity and redistribute more volume to the gastrointestinal system for digestive secretions.