Stabilizing effects of some amino acids on membranes of rabbit erythrocytes perturbed by chlorpromazine.
Hemolysis experiments indicated that glycine (20 mM) remarkably suppressed the chlorpromazine (CPZ)-induced osmotic permeability enhancing effect in rabbit erythrocytes. Lysine and aspartic acid also showed a similar protecting effect at the same concentration. Thus, the acid-base properties of amino acids were not a determining factor in stabilizing the cell membranes perturbed by CPZ. These results suggest that amino acids stabilize the membranes of the erythrocytes by inhibiting the osmotic water transfer from the outside to the inside of the cells. The kinetic studies in isotonic suspensions of erythrocytes indicated that glycine decreased the hemolytic activity of CPZ, and it was suggested that glycine molecules possibly inhibited penetration of CPZ into the cell membranes. The data also showed that the membrane stabilizing action of glycine was not affected by the dissociation of CPZ molecules. The degree of dissociation of glycine molecules was not found to be related to the degree of the protection. The FT-IR spectroscopy data indicated that glycine made the acyl chains of the liposome perturbed by CPZ more orderly.
Takeuchi
Y
Y
Faculty of Pharmaceutical Science, Kobe-Gakuin University Arise, Japan.
Yamaoka
Y
Y
Morimoto
Y
Y
Kaneko
I
I
Fukumori
Y
Y
Fukuda
T
T
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000648:ultrastructure; D005998:Glycine / Q000494:pharmacology; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008239:Lysine / Q000494:pharmacology; D009996:Osmotic Fragility / Q000187:drug effects; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013997:Time Factors
D000596:Amino Acids; D007038:Hypotonic Solutions; D001224:Aspartic Acid; D012965:Sodium Chloride; D008239:Lysine; D005998:Glycine; D002746:Chlorpromazine