Effects of diltiazem on the physicochemical properties of rat erythrocyte and liposome membrane: Comparison with pentoxifylline and propranolol.

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概要

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• In vitro effects of the coronary vasodilator diltiazem on rat erythrocytes and liposomes were studied in comparison with propranolol and pentoxifylline. Diltiazem improved the deformability of rat erythrocytes, reduced the viscosity of rat erythrocyte suspensions, and protected the erythrocyte against hypotonic hemolysis at concentrations above 10<SUP>-4</SUP> M, 10<SUP>-5</SUP> M and 5×10<SUP>-7</SUP> M, respectively. Diltiazem at 5×10<SUP>-4</SUP> M also improved the impaired deformability of ATP-depleted erythrocytes, whereas it affected neither the adenine nucleotide level nor the phosphorylation of spectrin in the erythrocytes. Diltiazem enhanced the interaction of 1-anilino-naphthalene-8-sulfonate, a fluorescent probe, with erythrocyte ghosts at concentrations above 5×10<SUP>-6</SUP> M and, above 5×10<SUP>-5</SUP> M, inhibited the (Na<SUP>+</SUP>+K<SUP>+</SUP>)-ATPase activity of the erythrocyte ghosts. Diltiazem reduced the microviscosity of both erythrocyte ghosts and liposomes prepared from rat erythrocyte lipids. Diltiazem induced aggregation of the liposomes prepared from rat erythrocyte lipids, phosphatidylserine or phosphatidylinositol, but it did not affect the liposomes prepared from a mixture of phosphatidylethanolamine and phosphatidylcholine (1:1). <I>l</I>-Diltiazem, a stereo-isomer of diltiazem, exhibited equipotent effects, compared with diltiazem, on these parameters. Propranolol showed similiar properties, but pentoxifylline shared none of the above properties, except that it improved the deformability of erythrocytes. From these results, it is suggested that diltiazem may affect the erythrocyte membrane by interacting with acidic phospholipids and thus reduce the microviscosity of the membrane, improve erythrocyte deformability and protects the erythrocyte against hypotonic hemolysis.

• 公益社団法人 日本薬理学会の論文

著者

• SASAKI Yasuhiko

  Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Takeyama Shigeyuki

  Pharmacological Research Laboratory Tanabe Seiyaku Co. Ltd.

• MORITA Takashi

  Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd.

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• METABOLISM OF TA-064,A NEW CARDIOTONIC AGENT : OXIDATION AND GLUCURONIDATION BY LIVER MICROSOMES
• Effects of diltiazem on the physicochemical properties of rat erythrocyte and liposome membrane: Comparison with pentoxifylline and propranolol.

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