MECHANISMS AND SITES OF MANNITOL PERMEABILITY OF SMALL AND LARGE-INTESTINE IN THE RAT

Mannitol is commonly used as an intestinal permeability probe, yet the mechanisms of its penetration of the intestinal barrier are nor entir ety clear. Therefore, we studied mannitol's permeability of different segments of the intestine and studied the kinetics and influence of in traluminal factors on mannitol permeability in vivo in perfused intest inal segments of rats. There was linear relationship between permeabil ity rate of mannitol and its luminal concentration (y = 7.2x + 1.7; r = 0.98), indicating that passive diffusion is involved in mannitol's p ermeability. Increased luminal fluid osmolarity front 0.3 to 0.6 osmol /liter resulted in decreased net waterflux with a corresponding decrea se in mannitol permeability in both jejunum and colon (P < 0.01), indi cating the prominent influence of solvent drag on net mannitol permeab ility. The relationship between mannitol permeability and water absorp tion at different osmolarities was linear in the jejunum and colon. At luminal osmolarity of 0.3 osmol/liter, 34.6% of mannitol permeability was mediated by passive diffusion and 65.4% was mediated by solvent d rag in the jejunum. Mannitol permeability was much more dependent on s olvent drag in the colon (88.9%) than in the small intestine (65.4%). The net permeability rate of mannitol was similar in the jejunum and i leum but was much higher in the colon (P < 0.01). Addition of chenodeo xycholate (5 mM) to the perfusate resulted in a significant decrease i n absorption of water (p < 0.01) with a corresponding decrease in mann itol permeability (P < 0.01). These studies indicate that mannitol per meability of the intestinal barrier is mediated by passive diffusion a nd solvent drag, with the latter accounting for a greater fraction of the total permeability.