Route of Access of Secretin into Rabbit Duodenal Lumen During Acid Perfusion

Abstract

The route of entry of immunoreactive secretin into the duodenal lumen during acid perfusion is unknown. Possible sites include paracellular diffusion from the extracellular space, transapical secretion from S cells, or leaching from cells damaged by the perfusate. Antisecretin in the extracellular space and interstitium should reduce access due to paracellular diffusion from the interstitium without significantly affecting secretion or leaching. We therefore studied the effect of intravenous antisecretin antibody on luminal secretin output. Two groups of rabbits received either intravenous normal rabbit serum (controls) or antisecretin antibody, before perfusing a closed segment of duodenum with hydrochloric acid. Preliminary experiments established that duodenal perfusion with HCl concentrations below 0.025N produced no apparent mucosal damage on electron microscopy. HCl concentrations above this significantly damaged the mucosa. In the control group, perfusion with 0.01N, 0.0125N, and 0.025N hydrochloric acid resulted in a dose-dependent increase in secretin in the perfusate. Secretin output was markedly reduced in the group injected with secretin antibody. Antisecretin antibody significantly reduced bile flow at all levels of HCl concentration in the duodenal perfusate. These data suggest that luminal secretin is probably derived from the interstitium and travels to the lumen across narrow paracellular channels.