MUTUAL EFFECTS OF AMINO-β-LACTAM ANTIBIOTICS AND GLYCYLGLYCINE ON THE TRANSMURAL POTENTIAL DIFFERENCE IN THE SMALL INTESTINAL EPITHELIUM OF RATS

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The transport mechanism of amino-β-lactam antibiotics across in vitro rat ileum was examined using the electrophysiological technique in comparison with that of dipeptides. The changes in the transmural potential difference (PD_t) induced by a series of amino-β-lactam antibiotics were correlated with the absorption percentage of these antibiotics from the in situ rat intestinal loops. On the contrary, β-lactam antibiotics without α-amino group such as dicloxacillin, methicillin and cefazolin did not induce such a stable change of PD_t. The changes in PD_t induced by cyclacillin (ACPC), cefadroxil (CDX) and glycylglycine (Gly-Gly) became saturable when the concentration of the substances increased. The half saturation concentration for ACPC, CDX, and Gly-Gly estimated from the changes in PD_t was nearly identical with that determined from influx of the substrates in the everted intestinal sacs. The mutual inhibition between amino-β-lactam antibiotics and Gly-Gly was observed in their induced PD_<tS>. The changes in PD_t induced by amino-β-lactam antibiotics were independent of those of glucose, glycine, and cefazolin. By the removal of Na^+ from the mucosal solution, the PD_t decreased one-fifth of the PD_t induced in the presence of Na^+. These results suggest that amino-β-lactam antibiotic-induced PD_t relates to the Na^+ ion fluxes as reported for dipeptides.
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