Abstract
The effect of protizinic acid (PRT), a non-steroidal antiinflammatory drug, on thein vivo leukokinin (LK) generation system using feline acute ischemia model,in vitro LK generation system and the LK-induced contraction of the isolated smooth muscle was investigated. When 3 mg/kg PRT was injected twice intravenously to cats with acute cardiac ischemia, increased blood acid protease activity was inhibited and significant inhibitory action on the decrease of leukokininogen, the precursor of LK, was observed. Simultaneously, ST-segment elevation on the electrocardiogram tended to be suppressed and the lowered mean aortic blood pressure was significantly restored. On the LK generation induced by rabbit kininogen and acid protease derived from mouse L-1210 leukemic cells or rabbit polymorphonuclear leukocytes, PRT showed a dosedependent inhibition while indomethacin (IM) and ibuprofen (IB) at a concentration of 3×10−4 M showed no effect. However, potencies of the inhibitory actions of PRT, IM and IB on the LK generation induced by bovine spleen cathepsin D were almost the same at a concentration of 3×10−4 M. Furthermore, PRT as well as IM showed antagonistic action on the isolated rat uterine contraction induced by LK. These results suggest that PRT not only inhibits thein vitro andin vivo generation of LK but also antagonizes to it on the receptor site of LK.
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References
E.A. Mueller, W.S.T. Griffin andK. Wildenthal,Isoproterenol-induced cardiomyopathy: changes in cardiac enzymes and protection by methylprednisolone, J. Mol & Cell. Cardiol.9, 565 (1977).
M.A. Ricciuti,Myocardial lysosomes stability in the early stage of acute ischemic injury, Am. J. Cardiol.30, 492 (1972).
M.J. Galvin andA.M. Lefer,Salutary effects of cysteine on cardiogenic shock in cats, Am. J. Physiol.235, H657 (1978).
M.L. Logan, J.H.R. Sutherland, T.K. Naranayan andL.M. Greenbaum,Effects of pepstatin on cathepsin D activity in the isolated guinea pig heart during hypoxia, Trans. Southeastern Pharmac. Soc.1, 40 (1980).
S. Roffman andL.M. Greenbaum,Properties of leukokininogen isolated from human neoplastic ascites, Biochem. Pharmac.28, 1043 (1979).
L.M. Greenbaum, Kininogenases of blood cells (alternate kinin generating systems). InHandbook of experimental Pharmacology, vol. 25, suppl.Bradykinin, Kallidin and Kallikrein, p. 91. (Ed.E.G. Erdös). Springer-Verlag, Berlin, Heidelberg and New York 1979.
A.M. Lefer andE.W. Polansky,Beneficial effects of ibuprofen in acute myocardial ischemia, Cardiology64, 265 (1979).
F. Sicuteri, G. Franchi, P.L. Del Bianco andM. Fanciullacci, Some physiological and pathological roles of kininogen and kinins. In Pro. Int. Symp.Hypotensive Peptides, p. 522 (EdsE.G. Erdös, N. Bach andF. Sicuteri). Springer-Verlag, New York 1966.
L.M. Greenbaum andT. Hosoda,Studies on the isolation of bradykininogen, Biochem. Pharmac.12, 325 (1963).
I. Ishikawa,Isolation of cathepsin D from human leukocyte, Biochim. biophys. Acta480, 228 (1977).
L.M. Greenbaum, P. Grebow, M. Johnston, A. Prakash andG. Semente,Pepstatin, an inhibitor of leukokinin formation and ascitic fluid accumulation, Cancer Res.35, 706 (1975).
L.M. Greenbaum andK.S. Kim,The kinin-forming and kininase activities of rabbit polymorphonuclear leukocytes, Br. J. Pharmac.29, 238 (1967).
P. Grebow, A. Prakash andL.M. Greenbaum,Leukokinin-H generation from human ascites fluid; its isolation and pharmacology, Agents and Actions9, 265 (1979).
J.T. Litchfield, Jr andF. Wilcoxon,A simplified method of evaluating dose-effect experiments, J. Pharmac. exp. Ther.96, 99 (1949).
H. Ohnishi, C. Ito, K. Suzuki andA. Saito,Experimental studies of the pharmacological effects of protizinic acid on bradykinin, J. Med. Soc. Toho29, 102 (1982).
K. Suzuki, Y. Kitamura, C. Ito andH. Ohnishi, Pharmacological studies on the protizinic acid. InAbstract of 8th International Congress of Pharmacology, p. 450. Tokyo 1981.
H. Ohnishi, C. Ito, K. Suzuki, Y. Kitamura, M. Shimora, A. Saito andR. Itoh,Effects of protizinic acid on the prostaglandin system and the production of oxygen radicals, Folia pharmac. jap.79, 561 (1981).
A. Saito, K. Suzuki andH. Ohnishi,Effects of protizinic acid on the leukocyte functions, J. Med. Soc. Toho29, 58 (1983).
L.M. Greenbaum, G. Semente, P. Grebow andS. Roffman,The isolation of leukokinin-H and leukokininogen from human ascites fluid; Their properties and role, Adv. Exp. Med. Biol.120B, 205 (1979).
L.M. Greenbaum,Leukocyte kininogenases and leukokinins from normal and malignant cells, Am. J. Path.68, 613 (1972).
H. Ohnishi, T. Sugawara, I. Fukuzawa, Y. Shibutani, C. Ito, S. Tsukuda andN. Ogawa,Toxicological and pharmacological studies of protizinic acid and its metabolites, Iyakuhin Kenkyu6, 408 (1975).
M.L. Ogletree andA.L. Lefer,Influence of nonsteroidal anti-inflammatory agents on myocardial ischemia in the cats. J. Pharmac. exp. Ther.197, 582 (1976).
L. Kaplan, J. Weiss andP. Elsbach,Low concentrations of indomethacin inhibit phospholipase A 2 of rabbit polymorphonuclear leukocytes, Proc. natn. Acad. Sci. USA75, 2955 (1978).
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Suzuki, K., Niho, T., Yamaguchi, K. et al. Effects of protizinic acid on leukokinin generation and its physiological action. Agents and Actions 14, 699–706 (1984). https://doi.org/10.1007/BF01978911
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DOI: https://doi.org/10.1007/BF01978911