天然生理活性物質の創薬科学への応用  [in Japanese] Application of physiologically active natural substances to sciences for creation of excellent medicines  [in Japanese]

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Author(s)

    • 大泉 康 OHIZUMI Yasushi
    • 東北大学薬学部生物薬品製造学教室 Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University

Abstract

In the course of our study on bioactive substances from marine organisms we found that eudistomin D derivatives isolated from the Caribbean tunicate <I>Eudistoma olivaceum</I> exhibited Ca releasing activities in skeletal muscle sarcoplasmic reticulum(SR). Our structure-activity relationship studies on eudistomin D derivatives indicate that bromoeudistomin D and 9-methyl-7-bromoeudistomin D are approximately 500 and 1, 000 times more potent than caffeine with regard to Ca releasing activity. Furthermore, we have successfully found that 4, 6-dibromo-3hydroxycarbazole, one of these analogues is a novel type of Ca release channel inhibitors.<BR> <SUP>3</SUP>H-MBED bound to the HSR in a replacable and saturable manner, indicating the existence of its specific binding site. Caffein competitively inhibited the <SUP>3</SUP>H-MBED binding to SR, suggesting that MBED shares the same binding site as that of caffeine.<BR> Myotoxin a (MYTX) has been found to induce Ca<SUP>2+</SUP> release having novel properties. <SUP>125</SUP>I-MYTX specifically bound to a single class of binding sites in SR. MYTX may binds to an important regulatory protein or channels of Ca release, which is not the ryanodine receptor, leading to Ca<SUP>2+</SUP> release from HSR.<BR> We have found that gingerol, xestoquinone and goniodomin A dramatically modified the functions of Ca<SUP>2+</SUP> pump (Ca<SUP>2+</SUP>-ATPase), myosin and actin, respectively, isolated from skeletal muscle to increase muscle contractility and have proven to be a valuable pharmacological tools for studies on muscle contraction.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 106, 61-66, 1995-09-01

    The Japanese Pharmacological Society

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