Because aspirin and the heavy metal salts of related anions have effects on intestinal ion transport and on diarrheal states, we have studied the effect of aspirin (ASA) on the in vitro rabbit ileum in an attempt to understand its mechanism of action. Ten millimolar of aspirin increased the conductance of rabbit ileum by 10-50% but did not change the permselectivity of the shunt path as determined by measurement of diffusion potentials. In Cl-free and HCO3-free solutions, aspirin reduced both Na absorption and the short-circuit current (Isc), which suggests an effect on electrogenic Na transport. Such an effect was not unexpected, since aspirin interferes with ATP production. However, in Ringer solution, aspirin in concentrations as little as 1 mM in the serosal solution reduced the Isc as before but also stimulated Na and Cl absorption and reduced JnetR (? HCO3 secretion) to zero. Aspirin had no effect on Na transport in the absence of Cl and no effect on Cl transport in the absence of Na, which suggests that aspirin stimulated a coupled transport process. Although these effects of ASA resemble those of α-adrenergic agents, ASA's effect was not blocked by α-adrenergic blockers such as phentolamine or phenoxybenzamine. The exact mechanism of ASA-stimulated NaCl absorption remains to be determined.
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