Electrophysiological studies on the mechanism for enhanced intestinal transport of water-soluble compounds by antibiotic peptide bacitracin

Citation
Ys. Quan et al., Electrophysiological studies on the mechanism for enhanced intestinal transport of water-soluble compounds by antibiotic peptide bacitracin, BIOL PHAR B, 22(8), 1999, pp. 841-845
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN journal
0918-6158 → ACNP
Volume
22
Issue
8
Year of publication
1999
Pages
841 - 845
Database
ISI
SICI code
0918-6158(199908)22:8<841:ESOTMF>2.0.ZU;2-E
Abstract
Bacitracin is an antibacterial cyclic dodecapeptide produced by Bacillus li cheniformin. Besides antibacterial activity, it is reported to have a prote ase inhibitory activity and an absorption enhancing action. Here we determi ned the effects of bacitracin on transport of water-soluble dye fluorescein isothiocyanate (FITC)-dextran across the rat intestinal mucosal membrane us ing an electrophysiological technique. Bacitracin enhanced the intestinal m ucosal-to-serosal transport of FITC-dextran in concentration-dependent and pH-dependent manners, In particular, the addition of bacitracin to the muco sal side led to a remarkable enhancement of FITC-dextran transport across t he colonic membrane. Furthermore, its exhibition of transport enhancement r equired the existence of metal divalent cations, Ca2+ and Mg2+, in the muco sal compartment. Electrophysiological study using voltage-clamp technique r evealed that a relatively lower concentration of bacitracin (5 mM) enhanced the transport of 6-carboxyfluorescein via a paracellular pathway in the co lonic membrane and higher concentration of bacitracin (20 mM) affects both transcellular and paracellular routes, resulting in significant enhancement of 5-carboxyfluorescein across the colonic membrane. These findings might provide the useful information for enhancing the intestinal transport of po orly absorbable drugs by bacitracin which has multiple functions.