天然生理活性物質の創薬科学への応用

• 大泉 康

  東北大学薬学部生物薬品製造学教室

書誌事項

タイトル別名

• Application of physiologically active natural substances to sciences for creation of excellent medicines

抄録

In the course of our study on bioactive substances from marine organisms we found that eudistomin D derivatives isolated from the Caribbean tunicate Eudistoma olivaceum 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> ³H-MBED bound to the HSR in a replacable and saturable manner, indicating the existence of its specific binding site. Caffein competitively inhibited the ³H-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 Ca²⁺ release having novel properties. ¹²⁵I-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 Ca²⁺ release from HSR.<BR> We have found that gingerol, xestoquinone and goniodomin A dramatically modified the functions of Ca²⁺ pump (Ca²⁺-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.

収録刊行物

• 日本薬理学雑誌

  日本薬理学雑誌 106 (supplement), 61-66, 1995

  公益社団法人 日本薬理学会

キーワード

• Pharmacology

詳細情報

• CRID: 1390282679247475840
• NII論文ID: 10008631255
• NII書誌ID: AN00198335
• DOI: 10.1254/fpj.106.supplement_61
• ISSN: 13478397
• ISSN: 00155691
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可