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Publikacije (125)

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T. Nakajima, G. Oshima, H. Yeh, R. Igić, E. G. Erdös

R. Igić, E. G. Erdös, H. Yeh, K. Sorrells, T. Nakajima

Angiotensin I converting enzyme or kininase II (DH) was purified from hog lung. The preparation was homogeneous in disc gel electrophoresis. Lung DH inactivated bradykinin and converted angiotensin I to angiotensin II. DH cleaved dipeptides in vitro from the C-terminal end of various substrates, including angiotensin I, bradykinin, B-chain of insulin, and shorter peptides, which were employed as substrates in spectrophotometric experiments. Several peptides, including glutathione, insulin, and the synthetic peptides SQ 20881 and peptide C, inhibited both plasma and lung DH. The latter inhibitors were inactive against carboxypeptidase N or kininase I. A sensitive and accurate assay of DH was developed, using 14C-DNS-Gly-Gly-Gly, a radioactive and fluorescent substrate. DH was coupled to Sepharose-4B to form a waterinsoluble complex. This insoluble enzyme cleaved both bradykinin and angiotensin I as determined by bioassay or radioimmunoassay. DH was also studied in the rat lung perfused in situ with (14C-Leu10)-angiotensin I and 14C-DNS-Gly-Gly-Gly substrates. During passage through the pulmonary circulation, half of the angiotensin I was converted to angiotensin II by the liberation of His-Leu; Gly-Gly was cleaved from the dansyl substrate. The activity of DH in the perfused lung of hypertensive rats was normal. Inhibitors such as insulin or SQ 20881 also blocked the action of DH in lung perfusion experiments.

S. Chiba, R. Igić, T. Nakajima

The effects of tremorine and oxotremorine were investigated in seven vagotomized dogs, using direct perfusion technique of the S-A node under constant perfusion pressure of 100mm Hg. 1) Tremorine (30 μg to 1mg) and oxotremorine (0.003 to 0.03 μg) injected into the sinus node artery induced a negative chronotropic effect. This negative chronotropic effect was blocked by atropine, but was not influenced by tetrodotoxin and propranolol. 2) Higher doses of oxotremorine produced long-lasting atrial fibrillation. At doses larger than 0.3 μg, oxotremorine induced atrial fibrillation in all animals. The induction and maintenance of atrial fibrillation were blocked by atropine. The induction was also prevented by a large amount of tetrodotoxin and propranolol in some animals. A large dose of propranolol occasionally blocked the maintenance of atrial fibrillation.

E. Erdos, R. Igić, H. Yeh, K. Sorrells, T. Nakajime

Abstract : Angiotensin 1 coverting enzyme or kininase 2 (dipeptide hydrolased(DH) was purified from hog lung. The preparation was homogeneous in disc gel electrophoresis. Lung DH inactivated bradykinin and converted angiotensin 1 to angiotensin 2. DH cleaved dipeptides in vitro from the C-terminal end of various substrates including angiotensin 1, bradykinin, B-chain of insulin and shorter peptides, which were employed as substrates in spectrophotometric experiments. Several peptides including glutathione, insulin and the synthetic peptides SQ 20881 and peptide C inhibited both plasma and lung DH. The latter inhibitors were inactive against carboxypeptidase N or kininase 1. DH cleaved both bradykinin and angiotensin 1 as determined by bio-assay or radio-immunoassay. DH was also studied in the rat lung. During passage through the pulmonary circulation half of the angiotensin I was converted to angiotensin 2 by the liberation of His-Leu; Gly-Gly was cleaved from the dansly substrate The activity of DH in the perfused lung of hypertensive rats was normal. Inhibitors such as insulin or SQ 20881 also blocked the action of DH in lung perfusion experiments. (Author)

R. Igić, H. Yeh, K. Sorrells, E. G. Erdös

R. Igić, P. Stern

Oxotremorine (0.125 mg/kg i.v.) did not produce a significant change in the "free" and "bound" brain acetylcholine in beri-beri pigeons, while in normal pigeons a significant increase was obtained. Oxotremorine caused tremor in normal pigeons. In beri-beri pigeons oxotremorine did not induce tremor but the compound potentiated beri-beri symptoms (opisthotonus and convulsions).

Oxotremorine (0.125 mg/kg) produces a significant increase in total acetylcholine content in whole pigeon brain. The contribution of different regions to this increase varies. The largest increase occurs in the nucleus basalis (paleostriatum augmentatum), a region which is highly involved in motor control. The mechanism by which oxotremorine increases the acetylcholine content of brain and the causal relationship between the rise in acetylcholine content and tremor are discussed.

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