Whale high-molecular-weight and low-molecular-weight kininogens

The expression of high-molecular-weight and low-molecular-weight kininogen mRNAs in the whale liver was examined by reverse transcription-polymerase c hain reaction. The nucleotide sequences of the high-molecular-weight and lo w-molecular-weight kininogen cDNAs were analyzed and deduced to the amino a cid sequences. The high-molecular-weight kininogen composed of 609 amino ac id residues with 18 signal peptides possessed the consensus sequences of th e cysteine protease inhibitor domains I and II, the bradykinin domain, the histidine-rich region, and the prekallikrein-binding region. Except for the histidine-rich region, the overall homologies with bovine, human, and rat high-molecular-weight kininogens were 81%, 76%, and 62%, respectively. The low-molecular-weight kininogen is composed of 408 amino acid residues. The nucleotide sequence down to C-1200 as well as the amino acid sequence till Ile(382) is identical to that of the high-molecular-weight kininogen. The r emaining low-molecular-weight kininogen-specific carboxy-terminal portion p ossessed an amino acid sequence similar to that of the land mammals. The ov erall homologies with bovine, human, and rat low-molecular-weight kininogen s were 82%, 79%, and 64%, respectively. The amino acid sequences of both wh ale high-molecular-weight and low-molecular-weight kininogens are most simi lar to those of the bovine among the land mammals analyzed so far. An incub ation of dolphin/whale plasma with human plasma kallikrein, or with bovine trypsin, in the presence of carboxypeptidase inhibitors generated bradykini n antigen as well as the spasmogenic activity to the estrous rat uterus. Th e amount of bradykinin released by the latter enzyme was almost double of t he former, indicating that the dolphin/whale plasma contained similar conce ntrations of low-molecular-weight and high-molecular-weight kininogens. (C) 2000 Elsevier Science Ltd. All rights reserved.