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Title: Identification and characterization of a new kallikrein-kinin system inhibitor from the salivary glands of the malaria vector mosquito Anopheles stephensi. Author: Isawa H, Orito Y, Iwanaga S, Jingushi N, Morita A, Chinzei Y, Yuda M. Journal: Insect Biochem Mol Biol; 2007 May; 37(5):466-77. PubMed ID: 17456441. Abstract: A new kallikrein-kinin system inhibitor, designated anophensin, was identified in the salivary glands of the malaria vector mosquito, Anopheles stephensi. In vitro reconstitution experiments showed that anophensin inhibits activation of the kallikrein-kinin system by inhibiting the reciprocal activation of factor XII (FXII) and prekallikrein (PK), and subsequent release of bradykinin. Additionally, anophensin inhibits activation of the kallikrein-kinin system on cultured human umbilical vein endothelial cells (HUVECs). Direct binding assays show that this inhibitory effect is due to Zn(2+)-dependent specific binding of anophensin to both FXII and high molecular weight kininogen (HK). Furthermore, anophensin interacts with both the N-terminus of FXII and domain D5 of HK, which are the binding domains for biological activating surfaces. These results suggest that anophensin inhibits activation of the kallikrein-kinin system by interfering with the association of FXII and HK with biological activating surfaces, resulting in the inhibition of bradykinin release in a host animal during insect blood-feeding.[Abstract] [Full Text] [Related] [New Search]