Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0082.
Fish Physiol Biochem. 1992 Dec;10(4):339-46. doi: 10.1007/BF00004483.
The cardiovascular effects of the kallikrein-kinin system (KKS) have not been completely characterized in lower vertebrates. In the present study, a specific, irreversible kallikrein inhibitor, Phe-Phe-Arg-chloromethyl ketone (PPACMK) was used to examine: 1. the role of the KKS in blood pressure regulation in vivo; 2. the nature of the pressor substance formed by the action of kallikrein on trout plasma in vivo and in vitro; and 3. the presence of kallikrein in trout gills and kidney. Dorsal aortic cannulated rainbow trout were used for in vivo blood pressure assays and two colorimetric serine-protease assays were used to examine tissue kallikrein activity. PPACMK alone had no effect on blood pressure in vivo. Pretreatment of porcine kallikrein with PPACMK inhibited the enzyme's pressor effect in trout by 80% and significantly attenuated the synthesis of vasopressor substance(s) from heat-treated trout plasma in vitro. Approximately 30% of gill serine protease activity was inhibited by pretreatment with PPACMK; no PPACMK-sensitive kallikrein activity was observed in the kidney. Salt water adaptation did not affect kallikrein-specific activity in the gill. These results show that the salmonid KKS does not appear to be involved in the regulation of systemic blood pressure. Further, the formation of pressor substances from trout plasma in vivo and in vitro is due to kallikrein activity and the peptides generated are similar. A kallikrein, similar to the mammalian enzyme, is found in trout gills, suggesting that the salmonid KKS may be a local mediator of gill function.
激肽释放酶-激肽系统(KKS)的心血管作用在较低等脊椎动物中尚未完全描述。在本研究中,使用一种特定的、不可逆的激肽释放酶抑制剂苯丙氨酰-苯丙氨酰-精氨酸-氯甲基酮(PPACMK)来研究:1. KKS 在体内血压调节中的作用;2. 激肽在体内和体外作用于鳟鱼血浆形成的升压物质的性质;3. 激肽在鳟鱼鳃和肾脏中的存在。背主动脉插管的虹鳟鱼用于体内血压测定,两种比色丝氨酸蛋白酶测定用于检测组织激肽释放酶活性。PPACMK 单独使用对体内血压没有影响。用 PPACMK 预处理猪激肽可抑制激肽在鳟鱼中的升压作用 80%,并显著减弱体外热处理鳟鱼血浆中血管加压物质的合成。用 PPACMK 预处理可抑制约 30%的鳃丝氨酸蛋白酶活性;在肾脏中未观察到对 PPACMK 敏感的激肽活性。海水适应不影响鳃中的激肽特异性活性。这些结果表明,鲑鱼 KKS 似乎不参与全身血压的调节。此外,体内和体外从鳟鱼血浆中形成的升压物质归因于激肽活性,生成的肽相似。在鳟鱼鳃中发现了一种类似于哺乳动物酶的激肽,这表明鲑鱼 KKS 可能是鳃功能的局部介质。