Relationship between the inotropy speeds in guinea-pig myocardium and lipophilic character of cardenolides and ericaceous toxins.

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概要

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• Interrelation between lipophilic characters and speeds of positive inotropic effect (PIE) of cardenolides and ericaceous toxins was studied by determining both parameters of lipophilicity and inotropy speeds. The lipophilic characters of 8 kinds of cardenolides, evaluated from RM<SUB>m</SUB>, or log k' values by means of thin layer chromatography (R<SUB>f</SUB>) or high performance liquid chromatography (retention time), increased in the order of ouabain, digoxin, digitoxigenin, digitoxigenin-mono-digitoxoside, digitoxigenin-bis-digitoxoside, digitoxin, α-acetyl-digitoxin, triacetyl-digitoxin. Lipophilic character, evaluated from R<SUB>m</SUB> values of 6 kinds of ericaceous toxins, was in decreasing order of 10S-grayanotoxin II, 6-acetyl grayanotoxin I, asebotoxin I, grayanotoxin I, asebotoxin III, asebotoxin X. The speed with which PIE developed was evaluated from the time to half maximum PIE (T<SUB>50</SUB>) of cardenolides and ericaceous toxins at a pD<SUB>2</SUB> concentration. The speed of positive inotropy of cardenolides was independent of their concentration tested in the range from half to twice the concentration of pD<SUB>2</SUB>, while the speeds of PIE of ericaceous toxins depended on their concentration in the same range used in case of cardenolides. Inotropy speed of these two classes of cardiotoxins correlated well with the lipophilic character: a) In the case of cardenolides, a positive and close correlation (r=0.98) was observed between T<SUB>50</SUB> and R<SUB>m</SUB>. The more lipophilic the cardenolides, the more time was required to reach the fully development of PIE. b) In contrast, a negative correlation (r=-0.82, between R<SUB>m</SUB> and T<SUB>50</SUB>) was obtained in the case of ericaceous toxins; Toxins with more lipophilic nature caused faster development of PIE. The present results can be interpreted to mean that the PIE receptor for cardenolides in myocardial cells is located on the outer surface of the sarcolemma, while that for ericaceous toxins is located on the inside of the myocardial cell.

• 公益社団法人 日本薬理学会の論文

著者

• Hotta Yoshihiro

  Department Of Ophthalmology Hamamatsu University School Of Medicine

• Shirai Naohiro

  Faculty Of Pharmaceutical Sciences Nagoya City University

• Takeya Kazumi

  Department Of Pharmacology Aichi Medical University

• Sakakibara Jinsaku

  Faculty Of Pharmaceutical Sciences Nagoya City University

• Ando Hiroaki

  Department Of Advanced Materials Chemistry Graduate School Of Engineering Yokohama National Universi

• Hotta Yoshihiro

  Department of Pharmacology, Aichi Medical University

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