JP6312191B2 - 血管弛緩作用を有するペプチド及び血管弛緩剤 - Google Patents
血管弛緩作用を有するペプチド及び血管弛緩剤 Download PDFInfo
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
北九州市保健福祉局医療部食肉センターより入手した、新鮮なブタ左冠状動脈前下行枝を主幹分岐部の約1cm下から約3cm採取し、あらかじめ混合ガス(95%O2、5%CO2)でバブリングし、氷冷したKrebs液(123mM NaCl、4.7mM KCl、15.5mM NaHCO3、1.2mM KH2PO4、1.2mM MgCl2、1.25mM CaCl2、11.5mM D−glucose)で動脈内の血液を洗浄した。採取当日に血管周辺の脂肪及び線維を取り除いた後、外膜を剥離し、Krebs液中にて4℃で保存した。実験当日、あらかじめ混合ガスでバブリングしたKrebs液中にて、血管を長軸方向に切り開き、綿棒を用い血管内腔を軽く一方向に擦って血管内皮細胞(内膜)を除去し、剃刀を用いて長軸方向に対して垂直に切断し平滑筋条片1mm×4mmを作製した。
弛緩作用を測定するための装置を図1に示す。ワイヤーの片側に平滑筋条片を吊るし、反対側をトランスデューサ(FDピックアップ:Panlab社製)に繋ぎ、増幅器(歪圧力用アンプ:Panlab社製)を通して記録計(卓上型ペンレコーダーU−603:パントス社製)で張力を検出した。平滑筋条片は、マグヌス管中の7mlのKrebs液に浸し、Krebs液は常に混合ガス(95%O2、5%CO2)でバブリングした。マグヌス管外は、恒温槽にて37℃に保った水を循環させた。また、交換用のKrebs液についても、37℃で保温し混合ガスをバブリングしたものを用いた。
上記試験装置を用い、Krebs液に10分間平滑筋条片を浸し、Krebs液を排出し、118mMの高カリウム溶液を加えて高カリウム脱分極による収縮を5分間引き起こし、その後高カリウム溶液を排出し、Krebs液に浸して10分間弛緩させる操作を繰り返し、高カリウム脱分極による収縮の安定性と大きさを指標に静止張力を最適化した。次に、高カリウム脱分極による収縮のトレースが安定したところで、40mMのカリウム溶液を加え、その収縮が定常状態に達した後、ブラジキニン(ペプチド研究所社製)を1μMとなるように加えて弛緩が生じなかったことで、血管内皮細胞が除去されていることを確認した。なお、血管内皮細胞が残っている場合、ブラジキニンを加えることで弛緩が生じる。
弛緩率を測定した結果を図3に示す。横軸が加えたペプチド濃度(mM)、縦軸が弛緩率である。図3に示すように、ペプチドB、C、Dは、血管弛緩作用を示し、ペプチドD、C、Bの順で弛緩率が高く、また弛緩効果は濃度依存的であった。具体的には、ペプチド濃度11.6mMの場合の弛緩率は、ペプチドAでは36%であるのに対し、ペプチドBでは52%、ペプチドC、Dは100%、ペプチド濃度5.8mMの場合の弛緩率は、ペプチドAでは21%であるのに対し、ペプチドBでは47%、ペプチドCでは45%、ペプチドDでは70%、ペプチド濃度1.16mMの場合の弛緩率は、ペプチドAでは9%であるのに対し、ペプチドBでは6%、ペプチドCでは13%、ペプチドDでは27%、ペプチド濃度0.58mMの場合の弛緩率は、ペプチドAでは0%であるのに対し、ペプチドBでは11%、ペプチドCでは5%、ペプチドDでは8%であった。
Claims (3)
- 分子内にアミノ酸配列Pro−Gly−Glyを有する、配列番号1〜3のいずれかに示されたアミノ酸配列からなるペプチドを有効成分とする血管弛緩剤。
- 分子内にアミノ酸配列Pro−Gly−Glyを有する、配列番号1又は3に示されたアミノ酸配列からなるペプチドを有効成分とする血流改善剤。
- 分子内にアミノ酸配列Pro−Gly−Glyを有する、配列番号3に示されたアミノ酸配列からなるペプチド。
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