TRANSCELLULAR FLUID SECRETION INDUCED BY CHOLERA-TOXIN AND VASOACTIVEINTESTINAL POLYPEPTIDE IN THE SMALL-INTESTINE OF THE RAT

The permeation of intravenously administered Cr-51-EDTA and [C-14]mann itol to the perfused intestinal lumen was measured in anaesthetized ra ts together with the net intestinal fluid. Net fluid secretion was ind uced by cholera toxin or by intravenous infusion of vasoactive intesti nal polypeptide (VIP). The plasma clearance of Cr-EDTA and mannitol wa s 0.9 +/- 0.1 and 1.4 +/- 0.2 mul min-1 g-1 intestine during the contr ol period prior to the secretion and the net fluid absorption was abou t 7 +/- 5 mul min-1 g-1. Cholera toxin induced a net fluid secretion o f about 30 +/- 7 mul min-1 g-1 but the clearance did not rise but decr eased significantly. The findings for VIP-induced secretion were simil ar. No indication of solvent drag was seen. Thus it is concluded that the fluid was secreted in channels which were smaller than the probes and we propose that the secreted fluid entered the intestinal lumen th rough the epithelial cells and not by the paracellular route. The decr eased permeation of Cr-EDTA and mannitol from plasma to lumen during v olume secretion suggest that there was a decreased mucosal permeabilit y during the secretion. The decrease in permeability was consistent wi th a decrease in pore size. One explanation of the data is that the po re radius contracted from about 35 to 15 angstrom during cholera if we assume a homogenous pore population. However, the data indicated that there was not a uniform size of the pore. A more plausible alternativ e is the presence of a small number of large pores (100 angstrom or mo re) which could decrease in size while the majority of pores had a con stant radius of about 15 angstrom.