The relationship between contractile tension and intracellular cyclic AMP level in frog atrium: an analysis by using NaF, verapamil and ouabain.
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Biomedical subjects
Publications and source records attributed to Y Abe.
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To investigate the mechanism of the cough-like reflex (CLR), we employed 1.1-dimethyl-4-phenylpiperazinium iodide (DMPP). In dogs anesthetized with alpha-chloralose, CLR was induced by administration of DMPP (i.v. and intracarotid arterial), lobeline and nicotine. Repeated administration of DMPP did not cause a tachphylaxis, however, lobeline and nicotine did induce a tachphylaxis. DMPP (i.a.), lobeline, nicotine and histamine caused an increase in respiratory resistance as measured by a Respiratory Resistance Meter, while DMPP (i.v.) did not. The ED50 of morphine, codeine, oxymethebanol, picoperidamine and piclobetol on CLR with DMPP was higher than that of those drugs employed for the peripherally-induced cough. CLR with DMPP was not affected by isoproterenol, ephedrine, atropine and propranolol. CLR was markedly depressed by hexamethonium and slightly depressed by benzonate. CLR was abolished after bilateral vagotomy or bilateral denervation of the carotid sinus nerves. These results indicate that the mechanism of CLR with DMPP is different from that of peripherally-induced cough and the carotid body chemoreceptor plays an important role in CLR with DMPP. This CLR may be useful for demonstrating the site of action and the mechanism of antitussive drugs.
The effects of N-ethylmaleimide (NEM), a sulfhydryl blocking reagent, on the membrane currents, action potentials and contractile tension in bullfrog atrial muscle were studied by using the double sucrose gap technique. In concentrations of 10(-3) to 10(-4) M, NEM led to a transient enhancement of twitch contraction followed by a late inhibition, while 10(-2) M NEM merely produced an inhibitory effect. The positive inotropism was accompanied by a prolongation of action potential and the negative inotropism, by a depression of action potential. Under voltage clamp conditions, 10(-3) M NEM reduced the fast inward current and increased the steady state outward and background currents. The slow inward current and the inward Ca current in Na-free conditions were transiently increased by 10(-3) M NEM with an enhancement of contractile tension. In voltage-tension relationships, NEM-induced augmentation of tension appeared in depolarizing pulses of 60--70 mV. The results indicate that NEM increases transiently the Ca conductance of the cell membrane. Preincubation with L-cysteine blocked the production of positive inotropic effect by NEM, suggesting that the effects of NEM are due to the blockade of protein sulfhydryl group in the atrial muscle.
The effects of N-ethylmaleimide (NEM) on the tension components of bullfrog atrium were studied under voltage clamp conditions using the double sucrose gap technique. NEM at a dilution of 10(-3) M inhibited the ICa-independent tonic tension elicited by large and long depolarizing pulses (140 mV, 2 sec) time-dependently, whereas the drug produced an initial transient increase and a later decrease of the ICa-dependent phasic tension elicited by small and short depolarizing pulses (60 mV, 100 msec). The effect of NEM was facilitated when the atrial muscles were exposed to a solution having either a reduced Na or an increased Ca concentration. In the presence of Mn ions, 10(-3) M NEM did not evidently inhibit tonic tension, and it led to a slight transient increase in phasic tension. NEM at 10(-3) M, which is known to inhibit sarcolemmal Na, K-ATPase, enhanced both the phasic tension and the tonic tension in the presence of ouabain and when perfused with K-free solution. Even under these conditions (10(-3) M NEM caused an initial transient decrease of ICa-independent tonic tension. This suggests that NEM has a different action on the atrial muscle from those of cardiac glycosides such as ouabain.
Four N-ethyl derivatives of kanamycin A and five N-ethyl derivatives of kanamycin B were synthesized. The antimicrobial activity of N-ethyl kanamycin derivatives was determined against aminoglycoside-sensitive and resistant organisms. The structure-activity relationship of these compounds is discussed with reference to the activity of N-acyl kanamycin derivatives.
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A new test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (N-BT-PABA) for an evaluation of exocrine pancreatic function was compared with a pancreozymin-secretin test in 38 subjects. Urinary recovery of PABA, which is absorbed from the intestine and conjugated in the liver after an oral administration of N-BT-PABA, depends mainly on chymotrypsin activity. The recovery rate of PABA in urine decreases in chronic pancreatitis, in which chymotrypsin activity in the duodenal juice is disturbed. The recovery rate of PABA in calcifying chronic pancreatitis was 40.2 +/- 15% and significantly less than 81.2 +/- 7.4% in normal subjects (P less than 0.01). The amount of PABA in urine during eight hours was correlated with parameters of volume output- bicarbonate concentration and amylase output stimulated by injections of pancreozymin and secretin (P-S test). The new test using N-BT-PABA is useful for the evaluation of exocrine pancreatic function in general practice.
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Effects of bumetanide (2.5, 25 and 250 microgram/kg i.v.) on renal hemodynamics and function were investigated in anesthetized dogs using clearance methods, stop-flow analysis and radioactive microsphere. Under conditions of mild isotonic saline loading, significant diuresis was observed within 5 min after the injection of 25 and 250 microgram/kg of the drug, and with the higher dose, a maximal fractional sodium excretion of 34% was observed. The dose of 250 microgram/kg of bumetanide caused a significant 44% increase in blood flow 5 min after the injection. In a hydropenic condition, the reabsorption of free water was significantly reduced, thus suggesting an inhibitory effect on the ascending limb of Henle's loop. In stop-flow experiments, inhibition of sodium reabsorption at the distal tubule was evident. Bumetanide increased blood flow in the juxtamedullary more so than in the superficial area. The increased blood flow in the juxtamedullary area also may contribute to the diuretic action of bumetanide through enhancement of the countercurrent exchange system in the renal medulla.
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