Mechanism of membrane damage induced by the amphipathic peptides gramicidin S and melittin.
The action of gramicidin S and melittin on human erythrocytes, Staphylococcus aureus and Escherichia coli was studied as an extension of the previous study (Katsu, T., Ninomiya, C., Kuroko, M., Kobayashi, H., Hirota, T. and Fujita, Y. (1988) Biochim. Biophys. Acta 939, 57-63). These amphipathic peptides stimulated the release of membrane phospholipids outside cells in a concentration range causing permeability change. The shape change of erythrocytes from normal discoid to spiculate form was observed just prior to the release of membrane components. We have proposed the following action mechanism of gramicidin S and melittin. The peptide molecules were predominantly accumulated in the outer half of the bilayer, deforming the erythrocyte cell into crenature. A large accumulation made the membrane structure unstable, resulting in the release of membrane fragments and the simultaneous enhancement of permeability. The action mechanism of these peptides was compared with that of simple surfactants.
Katsu
T
T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Kuroko
M
M
Morikawa
T
T
Sanchika
K
K
Fujita
Y
Y
Yamamura
H
H
Uda
M
M
D001514:Bee Venoms / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006096:Gramicidin / Q000494:pharmacology*; D006801:Humans; D008555:Melitten / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D001514:Bee Venoms; D010455:Peptides; D010743:Phospholipids; D015221:Potassium Channels; D006096:Gramicidin; D008555:Melitten