Acid-sensing protective mechanisms of duodenum.
The proximal duodenal mucosa, exposed to frequent pulses of gastric acid, is functionally "leaky", increasing the importance of defense mechanisms such as the mucus gel layer, cellular acid/base transporters, bicarbonate secretion, and mucosal blood flow. Our laboratory has used a unique in vitro perfused microscopic system to measure thickness of the adherent mucus gel (MGT), intracellular pH (pHi), bicarbonate secretion, and mucosal blood flow in anesthetized rats. Exposure to pulses of luminal acid, mimicking the rapid physiologic shifts of luminal pH, increases MGT and blood flow, and induces cellular bicarbonate loading, the latter followed by augmented bicarbonate secretion. The mechanism by which the epithelium senses luminal acid includes capsazepine-inhibitable vanilloid receptors, presumably similar to the vanilloid receptor TPVR-1. CFTR, the cAMP-regulated anion channel mutated in the disease cystic fibrosis, plays an essential role in duodenal bicarbonate secretion. Our data are consistent with the hypothesis that cellular bicarbonate loading is an important means of preserving epithelial pHi during luminal acid challenge. Increased MGT may damp rapid shifts of luminal pH. Enhanced mucosal blood flow plays a significant role in the removal of back-diffusing acid. These neurally coordinated systems act coherently to defend the vulnerable duodenal epithelial cells from concentrated gastric acid.
Kaunitz
J D
JD
Greater Los Angeles Veteran Affairs Healthcare System, WLAVA Medical Center, Los Angeles, CA, USA. jake@ucla.edu
Akiba
Y
Y
D000818:Animals; D004386:Duodenum / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009092:Mucous Membrane / Q000166:cytology / Q000378:metabolism / Q000502:physiology