Amphotericin B-induced ion flux is markedly attenuated in phosphatidylglycerol membrane as evidenced by a newly devised fluorometric method.
The effect of phospholipid head group on the membrane-permeabilizing activity of amphotericin B (AmB) was examined using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG) liposomes. The activity of AmB was evaluated as K(+) influx measured as pH change inside liposomes by fluorescent measurements of 2',7'-bis(carboxyethyl)-4 or 5-carboxyfluorescein (BCECF). AmB showed prominent permeability in POPC liposomes, whereas hardly inducing ion flux in POPG membrane. POPC added to POPG liposomes as a minor constituent markedly enhanced membrane permeability, indicating the importance of a phosphonocholine group of PC for the drug's activity.
Takano
Tetsuro
T
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Konoki
Keiichi
K
Matsumori
Nobuaki
N
Murata
Michio
M
D000666:Amphotericin B / Q000737:chemistry* / Q000378:metabolism; D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D005470:Fluorometry / Q000379:methods*; D017136:Ion Transport; D008081:Liposomes / Q000378:metabolism*; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*
D000935:Antifungal Agents; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D000666:Amphotericin B; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine