Electrophysiological studies on the mechanism for enhanced intestinal transport of water-soluble compounds by antibiotic peptide bacitracin.
Bacitracin is an antibacterial cyclic dodecapeptide produced by Bacillus licheniformin. Besides antibacterial activity, it is reported to have a protease inhibitory activity and an absorption enhancing action. Here we determined the effects of bacitracin on transport of water-soluble dye fluoresceinisothiocyanate (FITC)-dextran across the rat intestinal mucosal membrane using an electrophysiological technique. Bacitracin enhanced the intestinal mucosal-to-serosal transport of FITC-dextran in concentration-dependent and pH-dependent manners. In particular, the addition of bacitracin to the mucosal side led to a remarkable enhancement of FITC-dextran transport across the colonic membrane. Furthermore, its exhibition of transport enhancement required the existence of metal divalent cations, Ca2+ and Mg2+, in the mucosal compartment. Electrophysiological study using voltage-clamp technique revealed that a relatively lower concentration of bacitracin (5 mM) enhanced the transport of 6-carboxyfluorescein via a paracellular pathway in the colonic membrane and higher concentration of bacitracin (20 mM) affects both transcellular and paracellular routes, resulting in significant enhancement of 6-carboxyfluorescein across the colonic membrane. These findings might provide the useful information for enhancing the intestinal transport of poorly absorbable drugs by bacitracin which has multiple functions.
Quan
Y S
YS
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Kuribayashi
D
D
Nakamoto
Y
Y
Doi
M
M
Muranishi
S
S
Fujita
T
T
Yamamoto
A
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001414:Bacitracin / Q000494:pharmacology*; D001692:Biological Transport; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D001414:Bacitracin; D016650:Fluorescein-5-isothiocyanate