Document 0727
 DOCN  M9610727
 TI    Osmotic stress sensitizes sterol-free phospholipid bilayers to the
       action of Amphotericin B.
 DT    9601
 AU    Wolf BD; Hartsel SC; Department of Chemistry, University of
       Wisconsin-Eau Claire; 54702-4004, USA.
 SO    Biochim Biophys Acta. 1995 Sep 13;1238(2):156-62. Unique Identifier :
       AIDSLINE MED/96038199
 AB    We have tested the ability of Amphotericin B to form ion
       channels/defects in osmotically stressed large unilamellar vesicles
       (LUV) using pyranine fluorescence detected ion/H+ exchange. We found
       that sterol-free LUV exhibit greatly increased sensitivity to AmB
       channel formation in the soluble oligomer state (> 0.5 microM) under
       modestly hypoosmotic conditions (< 100 delta mosM). These vesicles are
       completely insensitive under isoosmotic conditions. The related
       antibiotics, Amphotericin B methyl ester and Nystatin showed almost no
       activity under hypoosmotic conditions in the absence of sterol. This
       difference may be attributable to differences in solution oligomeric
       states. Experiments with KCl and CaCl2 internal buffers demonstrate that
       these sterol-free AmB membrane disruptions are highly selective for
       monovalent cations (K+) over anions (Cl-), ruling out massive lysis or
       unselective membrane defects caused by osmotic pressure. Thus, AmB seems
       to be acting as a 'molecular harpoon', an expression coined to describe
       substances which can selectively target osmotically stressed, strained
       or highly curved membranes. These results may provide a rationale for
       AmB's reported anti-HIV activity and reported activity against
       sterol-free small unilamellar vesicles (highly curved membranes) as well
       as the reduced activity of liposomal drug delivery systems toward
       cholesterol-containing and sterol-free membranes (fewer soluble
       oligomers).
 DE    Amphotericin B/*PHARMACOLOGY  Calcium/METABOLISM  Chlorides/METABOLISM
       Hydrogen-Ion Concentration  Ion Channels/METABOLISM  Ion Transport
       *Lipid Bilayers  Osmotic Pressure  Phospholipids/*METABOLISM
       Potassium/METABOLISM  Sterols/METABOLISM  Support, Non-U.S. Gov't
       Support, U.S. Gov't, Non-P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).