Modulation of polymyxin b effects on mammalian urinary bladder.
Berg, Jamie R., Christian M. Spilker, and Simon A. Lewis.
Department of Physiology and Biophysics, University of Texas
Medical Branch, Galveston, Texas 77555
APStracts 5:0083F, 1998.
This report demonstrates that Ca2+, Mg2+ and protons alter the ability
of polymyxin B (PX, a cationic antibiotic used clinically as a
bactericidal agent), to increase the apical membrane conductance of
the rabbit urinary bladder. Using electrophysiological methods, it
was determined that these alterations occur by two mechanisms. First,
they blocked the PX-induced conductance in a rapid and reversible
manner. Second they competed with PX for a membrane binding site. In
addition, Ca2+ (but not Mg2+ or protons) altered the rate at which
the induced conductance could be reversed. When solution pH was
greater than 8.8, PX was not able to induce a conductance. This
ability of high pH to inhibit the action of PX was due to a decrease
in the number of positive charges on PX. Further studies demonstrated
that for maximal-activity, PX required its fatty acid tail. These
data were used to develop a model describing the mechanism by which
PX can induce a conductance in the apical membrane of the rabbit
urinary bladder.
Received 22 December 1997; accepted in final form 8 April 1998.
APS Manuscript Number F401-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 24 April 1998