Localization of Tissue Plasminogen Activator on Experimental Microthrombi in Rats. Microautoradiographic Observations

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概要

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• The localization of tissue plasminogen activator (t-PA) on microthrombi in various organs of disseminated intravascular coagulation rats (DIC rats) was investigated by using microautoradiographic technique. After the injection of [^<125>I] fibrinogen, experimental DIC rats induced by the infusion of thrombin for 1 h were submitted to microautoradiograms (MARGMs) of some major organs. The radioactivity of [^<125>I] fibrin thrombi, which were observed as silver grains, was localized in the glomeruli and parts of small vessels in the kidney. In the liver, microthrombi were seen in sinusoid vessels and on Kupffer cells. In addition, many microthrombi were noted in small vessels in the lung and marginal zones in the spleen. Two min after the intravenous administration of [^<125>I] t-PA to DIC rats, many silver grains were observed on each MARGM of the kidney, lung, liver and spleen showing the formation of microthrombi. From the identical results with the observations of MARGMs after the injection of [^<125>I] fibrinogen, we confirmed that t-PA was highly accumulated to microthrombi formed in small vessels of the organs. The scattered silver grains were widely observed on the hepatocytes. This result suggested that t-PA bound to the parenchymal cell surface might be transported into the hepatocytes by receptor-mediated endocytosis. On the other hand, when [^<125>I] urokinase plasminogen activator ([^<125>I] u-PA) was administered intravenously to DIC rats, many silver grains were observed on MARGM of the proximal tubules in the kidney but not seen on MARGMs of the glomeruli in the kidney, nor in the lung, liver, and spleen. This observation suggested that u-PA might not have a characteristic to accumulate to thrombi.

• 公益社団法人日本薬学会の論文

著者

• Kondo S

  Nippon Hoechst Marion Roussel Ltd.

• Koide T

  Faculty Of Pharmaceutical Sciences Osaka University

• Koide Takashi

  Tokyo Research Laboratories Kowa Co. Ltd.

• KANDA Hiroyasu

  日産化学工業株式会社中央研究所

• KIMATA Hideki

  興和株式会社東京研究所

• Kimata H

  Kowa Company Ltd. Tokyo

• KIMATA Hideki

  Tokyo Research Laboratories, Kowa Co., Ltd.

• NAKAJIMA Katsuaki

  Tokyo Research Laboratories, Kowa Co., Ltd.

• KONDO Syuhei

  Tokyo Research Laboratories, Kowa Co., Ltd.

• Nakajima K

  Tokyo Research Laboratories Kowa Co. Ltd.:asahi Chemical Industry Co. Ltd.

• Nakajima Katsuaki

  Tokyo Research Laboratories Kowa Company Ltd.

• Koshi T

  Tokyo Research Laboratories Kowa Co. Ltd.

• Kimata Hideki

  Tokyo Research Laboratories, Kowa Co. Ltd.

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