Contraction of the large conductance coronary artery produced by acetylcholine in the mini pig.
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Acetylcholine↗
Biomedical subjects
K Takeda
Publications and source records attributed to K Takeda.
Effects of extracellular sodium concentration on null potential, conductance and open time of endplate channels.
(i) Effects of extracellular sodium concentration, [Na]o, on endplate channel characteristics were investigated in voltage-clamped, glycerol-treated toad sartorius fibres. (ii) The relation between [Na]o (and [K]o) and acetylcholine null potential could be reasonably well fitted by the Goldman-Hodgkin-Katz type of equation, except when [Na]o was higher than normal. Anions had no significant effect on the null potential. (iii) Endplate channel open time (phi), whether measured from miniature endplate currents or from current fluctuations induced by iontophoresis of acetylcholine, varied inversely with [Na]o. The relation between phi-1(= alpha) and [Na]0 could be fitted by alpha = alpha max [Na]o/(Km + [Na]o) with a Km of 92 mM. (iv) Endplate conductance, measured at the peak of endplate currents or at the peak of spontaneous miniature endplate currents, increased nonlinearly with [Na]o. (v) Single channel conductance, gamma, also increased nonlinearly with [Na]o. Experimental observations at -90 mV could be fitted by the relation gamma = gamma max [Na]o/(Km + [Na]o), giving values for gamma max and Km of 47 pS and 146 mM respectively. Correcting channel conductance for the contribution from potassium ions gave values of gamma max and Km of 78 pS and 423 mM respectively. (vi) The results are consistent with the hypothesis that binding sites for Na ions can modulate both channel lifetime and conductance and that these sites become saturated at higher sodium concentrations.
Acetylcholine↗
[Endogenous androgen levels of human prostatic tissues].
Endogenous androgen levels of prostatic tissues in patients with benign prostatic hypertrophy (BPH) and untreated prostatic cancer (PC) were determined by radioimmunoassay using sephadex LH-20 column chromatography. By this assay procedure, it was possible to measure tissue androgen levels with only 30 approximately 40 mg weight of tissues. In BPH (n=20) the concentrations of steroids (mean +/- standard deviation, ng/g. tissue weight) were 5 alpha-androstane 3 alpha, 17 beta diol (A-diol), 2.31 +/- 1.29; dihydrotestosterone (DHT), 4.97 +/- 2.17; testosterone (T), 0.62 +/- 0.33. In PC (n=17) the concentrations were 5.51 +/- 3.23; 3.94 +/- 3.16; and 0.93 +/- 0.38; respectively. The concentrations of DHT were raised and the levels of A-diol were reduced significantly (P less than 0.01) in BPH compared with PC. Tissue DHT levels of PC were variable, but they could be classified in to two groups. One was below 2 ng levels (n=8) similar to those of non-androgen target tissues and the other was over 2 ng (n=19). The relationships between histological differentiation and tissue DHT levels in prostatic cancer were examined. In poorly differentiated cancer (n=4), DHT levels were low in all cases, furthermore even in well differentiated ones there were 4 cases with levels below 2 ng. Thus, the measurement of endogenous DHT levels of prostatic tissues was considered to be valuable for the judgment of androgen dependency in prostatic cancer.
Aged↗
Photoreaction of tyrosine-iodinated bacteriorhodopsin at low temperature.
To elucidate the role of tyrosine residues in the shift of lambda max and the light-driven proton pump of bacteriorhodopsin, the photochemical reaction of tyrosine-iodinated bacteriorhodopsin (tyr-mod-bR) was investigated by low-temperature spectrophotometry. After 4-5 of 11 tyrosine residues of bacteriorhodopsin were iodinated, the meta-intermediate of tyr-mod-bR in 75% glycerol solution became so stable that its decay could be observed even at room temperature and it was stable in the dark for several hours at -65 degrees C. Four batho-intermediates were formed by irradiation with green light (500 nm) at -170 degrees C. Like native bacteriorhodopsin, these batho-intermediates were photoreversible at -170 degrees C. Four corresponding meta-intermediates were also formed by irradiation at -60 degrees C. Using the difference spectra between meta-intermediates and tyr-mod-bR, the absorption spectra of four kinds of tyr-mod-bRs, batho-intermediates, and meta-intermediates were estimated. Each was at shorter wavelengths than that of its corresponding type in native bacteriorhodopsin. The results indicate that two or more tyrosine residues have some role in determining color in native bacteriorhodopsin.
Bacteriorhodopsins↗
Effects of divalent cations on toad end-plate channels.
Miniature end-plate currents (MEPCs) and acetylcholine-induced current fluctuations were recorded in voltage-clamped, glycerol-treated toad sartorius muscle fibers in control solution and in solutions with added divalent cations. In isosmotic solutions containing 20 mM Ca or Mg, MEPCs had time constants of decay (tau D) which were about 30% slower than normal. In isotonic Ca solutions (Na-free), greater increases in both tau D and channel lifetime were seen; the null potential was -34 mV, and single-channel conductance decreased to approximately 5 pS. Zn or Ni, at concentrations of 0.1-5 mM, were much more effective in increasing tau D than Ca or Mg, although they did not greatly affect channel conductance. The normal temperature and voltage sensitivity of tau was not significantly altered by any of the added divalent cations. Surface potential shifts arising from screening of membrane fixed charge by divalent cations cannot entirely explain the observed increases in tau, especially when taken together with changes in channel conductance.
Acetylcholine↗
Hybrid ATPase's formed from subunits of coupling factor F1's of Escherichia coli and thermophilic bacterium PS3.
ATPase complexes were reconstituted from homologous and heterologous combinations of alpha, beta, and gamma subunits of coupling factor ATPase TF1 of thermophilic bacterium PS3 and EF1 of Escherichia coli. TF1 and alpha beta gamma complex reconstituted from TF1 subunits were thermostable and activated by methanol, sodium dodecyl sulfate and anions and they were halophilic, whereas EF1 and its three-subunit complex did not show these properties. The hybrid ATPase alpha T beta T gamma E (complex of the alpha and beta subunits of TF1 and the gamma subunit of EF1) showed closely similar properties to TF1 except for thermostability, while alpha E beta E gamma T (alpha and beta from EF1 and gamma from TF1) had similar properties to EF1. These results suggest that alpha and/or beta is required for the properties of F1. The complex alpha E beta T gamma E showed similar properties to EF1 except for its optimum pH: this complex had a broad pH optimum at about pH 7, whereas EF1 had an optimum at pH 8.5. No hybrid complexes were thermostable, suggesting that all three subunits of TF1 are required for heat stability. These hybrids showed higher halophilicity than EF1, although they were less halophilic than TF1. The hybrid enzymes studied here are the first thermophilic-mesophilic hybrid enzymes obtained.
Adenosine Triphosphatases↗
Reactions of a fluorescent ATP analog, 2'-(5-dimethyl-aminonaphthalene-1-sulfonyl) amino-2'-deoxyATP, with E. coli F1-ATPase and its subunits: the roles of the high affinity binding site in the alpha subunit and the low affinity binding site in the beta subunit.
We performed kinetic studies on the reactions of a fluorescent ATP analog, 2'-(5-dimethyl-aminonaphthalene-1-sulfonyl) amino-2'-deoxyATP (DNS-ATP), with E. coli F1-ATPase (EF1) and its subunits, to clarify the role of each subunit in the ATPase reaction. The following results were obtained. 1. One mol of EF1, which contains nonexchangeable 2 mol ATP and 0.5 mol ADP, binds 3 mol of DNS-ATP. The apparent dissociation constant, in the presence of Mg2+, was 0.23 microM. Upon binding, the fluorescence intensity of DNS-ATP at 520 nm increased exponentially with t1/2 of 35 s, and reached 3.5 times the original fluorescence level. Following the fluorescence increase, DNS-ATP was hydrolyzed, and the fluorescence intensity maintained its enhanced level. 2. The addition of an excess of ATP over the EF1-DNS-nucleotide complex, in the presence of Mg2+, decreased the fluorescence intensity rapidly, indicating the acceleration of DNS-nucleotide release from EF1. ADP and GTP also decreased the fluorescence intensity. 3. DCCD markedly inhibited the accelerating effect of ATP on DNS-nucleotide release from EF1 and the EF1-DNS-ATPase or -ATPase activity in a steady state. On the other hand, DCCD only slightly inhibited the fluorescence increase of DNS-ATP, due to its binding to EF1, and the rate of single cleavage of 1 mol of DNS-ATP per mol of alpha subunit of EF1. 4. In the presence of Mg2+, 0.65-0.82 mol of DNS-ATP binds to 1 mol of the isolated alpha subunit of EF1 with an apparent dissociation constant of 0.06-0.07 microM. Upon binding, the fluorescence intensity of DNS-ATP at 520 nm increased 1.55 fold very rapidly (t1/2 less than 1 s). No hydrolysis of DNS-ATP was observed upon the addition of the isolated alpha subunit. The fluorescence intensity of DNS-ATP was unaffected by the addition of the isolated beta subunit. DNS-ATP was also unhydrolyzed by the isolated beta subunit. 5. EF1-ATPase was reconstituted from alpha, beta, and gamma subunits in the presence of Mg2+ and ATP. The kinetic properties of the fluorescence change of DNS-ATP in the reaction with the reconstituted EF1-ATPase were quite similar to those of native EF1. Most of our findings are consistent with a simple mechanism that the high affinity catalytic site and low affinity regulatory site exist in the alpha subunit and beta subunit, respectively. However, the findings mentioned in (4) suggest that the binding of the alpha and beta subunit, which is mediated by the gamma subunit, induces conformational change(s) in the ATP binding site located probably in the alpha subunit, and that the conformational change(s) is essential to exert the full hydrolyzing activity.
Adenosine Triphosphate↗
Non-adrenergic inhibitory nerves and putative transmitters in the smooth muscle of cat trachea.
1. Effects of non-adrenergic non-cholinergic inhibitory nerve stimulation on the smooth muscle of the cat trachea were studied in vitro using micro-electrode, double sucrose-gap and tension recording methods.2. Electrical field stimulation with a short pulse (50 mus) evoked an excitatory junction potential (e.j.p.) followed by a twitch, with or without a subsequent small, long-lasting relaxation. This response was abolished by tetrodotoxin (5 x 10(-7) M).3. After pre-treatment with atropine (10(-7) to 5 x 10(-6) M) both e.j.p. and twitch tension were selectively blocked and repetitive stimuli at 20 Hz evoked in some preparations slow membrane hyperpolarization followed by long-lasting relaxation. These effects were abolished by propranolol (2 x 10(-6) M). In the presence of atropine (10(-6) M) and propranolol (2 x 10(-6) M) field stimulation caused no detectable change in tension, membrane potential or membrane resistance.4. 5-Hydroxytryptamine (5-HT) (10(-6) to 5 x 10(-6) M) produced a tonic contracture of the cat trachea. In the presence of atropine, field stimulation induced a marked reduction in the amplitude of the contracture which was only partly suppressed by propranolol (5 x 10(-6) M). During this muscle relaxation, produced by field stimulation in the presence of 5-HT, atropine and propranolol, there was no apparent change in the membrane potential or in membrane resistance. The magnitude of the relaxation was proportional to the number of stimuli applied.5. ATP (< 10(-3) M) and VIP (< 10(-9) M) had no effect on the membrane potential or resistance of the smooth muscle cells of the cat trachea, although higher concentrations of VIP (> 10(-8) M) hyperpolarized the membrane and reduced the membrane resistance. Low concentrations, i.e. ATP 5 x 10(-6) M or VIP 10(-12) M, which had no effects in the electrical membrane properties, caused relaxation of the muscle contracture evoked by 5-HT.6. After desensitization to exogenous ATP or adenosine, in the presence or absence of dipyridamole (2 x 10(-7) M), the amplitude of the muscle relaxation evoked by the activation of non-adrenergic inhibitory nerves was not affected. It was, however, much smaller during partial desensitization to VIP.7. These results indicate that cat tracheal smooth muscles are innervated by non-adrenergic, non-cholinergic inhibitory nerves, which cause muscle relaxation without affecting the electrical membrane properties. The possible involvements of ATP or VIP in the inhibitory nervous transmission is discussed.
Adenosine Triphosphate↗
Endogenous brain angiotensin II-mediated sympathetic nerve responses are not augmented in mature spontaneously hypertensive rats.
Conjugated estrogens injected into the lateral brain ventricle in awake rats elicited behavioral excitation and vasopressor responses. Magnitude of pressor responses was greater in spontaneously hypertensive rats (SHR) than in normotensive Kyoto Wistar rats (WKY). Pressor responses in SHR were abolished by central pretreatments of either captopril or angiotensin II analog. Under urethane anesthesia, conjugated estrogens still produced greater pressor responses in SHR, but accompanying increases in sympathetic nerve firings were the same in both WKY and SHR. These results suggest that while centrally-administered estrogens may activate the brain renin-angiotensin system to increase sympathetic nerve firing and thereby elevated blood pressure, SHR have larger pressor responses only because peripheral vascular reactivity has been increased.
Angiotensin II↗
The role of brain angiotensin II in the mechanism of the pressor responses to intracisternal injection of hypertonic NaCl in urethane anesthetized rats.
Intracisternal injections of hypertonic NaCl elicited the pressor responses in urethane anesthetized spontaneously hypertensive and normotensive Wistar rats. The intracisternal pretreatment of 1-Sar-8-Ile-angiotensin II, angiotensin II analog, could abolish the pressor responses to intracisternal injections of 5% NaCl in urethane anesthetized spontaneously hypertensive rats, while basal blood pressure was not affected by these pretreatment. Both intracisternal and intravenous administration of captopril, an angiotensin I converting enzyme inhibitor, did not alter the pressor effect of hypertonic NaCl in normotensive rats. Basal blood pressure was lowered by intravenous injection of captopril. The involvement of angiotensin II in the pressor mechanism of hypertonic NaCl was confirmed by the enhanced pressor responses to intracisternal injections of 5% NaCl in urethane anesthetized rats pretreated intracisternally with angiotensin II. These findings suggest that angiotensin II itself could play an important role in the pressor responses to intracisternal injections of hypertonic NaCl without involving a converting enzyme system.
1-Sarcosine-8-Isoleucine Angiotensin II↗
A comparison of antihypertensive effects of atenolol and propranolol in the spontaneously hypertensive, DOCA/saline hypertensive and renal hypertensive rats.
Antihypertensive effects of a long-term oral regimen of atenolol were studied in SHR, DOCA/saline hypertensive and renal hypertensive rats (one kidney, one clip) in comparison with the effects of propranolol. Both the beta-blockers prevented the development of hypertension in SHR but did not affect that in DOCA/saline and renal hypertensive rats. Both of the beta-blockers produced no acute hypotensive effects on the established DOCA/saline and renal hypertension of the rat, although they produced a decrease in the heart rate.
Animals↗
Effect of sodium loading and depletion on cyclic nucleotides in plasma and aorta. Interaction between prostacyclin and cyclic nucleotides.
The present study evaluated the effect of sodium loading and sodium depletion on cAMP and cGMP content of rat aorta. Enhanced generation of prostacyclin (PGI2) in aorta was noticed in sodium loading and sodium-depletion. As PGI2 is potent vasoactive agent, the interaction between PGI2 generation in the aorta and cyclic nucleotide accumulation in the aorta was investigated. Sodium depletion of rats induced the elevation of both cAMP and cGMP in the aorta and of cAMP in plasma. No change in cyclic nucleotides was noticed following sodium loading. These changes in cyclic nucleotides were felt to reflect the fluctuation of vasoactive agents under various sodium metabolism conditions. These observations may indicate that PGI2 is not a major factor in the regulation of cyclic nucleotide metabolism under sodium loading and sodium depletion. The increased accumulation of cAMP and cGMP in rat aorta in sodium depletion may be due to the cumulative effects of PGI2, catecholamine and probably angiotension II which are induced by sodium depletion.
Aldosterone↗
Enhanced vascular reactivity to norepinephrine in salt-sensitive patients with hypertension.
Twenty patients with hypertension were studied under diets containing low and high salt to identify factors which might be involved in elevating blood pressure under sodium-loading. They were classified as "salt-sensitive" (SS) and "nonsalt-sensitive" (NSS) according to the presence or absence of greater than 10% increases in mean blood pressure when a low salt diet was replaced by a high salt diet. During high-sodium intake, the SS patients showed reduced urinary excretion of sodium and elevated plasma levels of aldosterone as compared with plasma renin activity. The SS patients also showed an enhanced pressor response to norepinephrine under both low-sodium and high-sodium diets. From these results, it is suggested that the sodium retention, which is probably related to nonsuppressed levels of PAC under sodium-loading, is one of the factors in elevating blood pressure in the SS patients. Moreover, the enhanced pressor response to norepinephrine seems to contribute, in part, to elevation of blood pressure in the SS patients under salt-loading.
Aged↗
Function of plasmids in the production of aureothricin. I. Elimination of plasmids and alteration of phenotypes caused by protoplast regeneration in Streptomyces kasugaensis.
The spontaneous mutant 18a derived from Streptomyces kasugaensis MB273 exhibited pleiotropic effect such as loss of aerial mycelium formation, aureothricin (AT) production, and of citrullin biosynthesis, as well as changes in plasmid; the mutant required cystine for production of aureothricin. An improved method of protoplast regeneration was applied to S. kasugaensis MB 273-18a and a regeneration efficiency of 90% or more was obtained. Sixty to ninety percent of the colonies regenerated from the 18a protoplasts exhibited reversion of the pleiotropic mutation in 18a. Moreover, of 13 regenerated strains which showed these drastic phenotypic variations, it was found that their plasmid types varied. These types could be divided into two groups; the RI type (5 strains) which contained a large amount of pSK2, a small amount of pSK3 and no pSK1, and the RII type (8 strains) in which no closed-circular DNA was detected. From these results, the following conclusions were obtained. First, plasmid curing in RII type strains and also the variation of plasmid copy in the RI type strains occurred as the result of protoplast regeneration. Second, the structural genes for biosynthesis of AT probably exist on chromosome. Third, regeneration of 18a protoplasts causes the reversion of pleiotropic mutation with high frequency. A working hypothesis was proposed to explain these complex phenomena.
Anti-Bacterial Agents↗
Hypotensive effect of nifedipine in hypertensive patients with chronic renal failure.
The hypotensive effect of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxydimethylester (nifedipine, Adalat) was studied in 15 hypertensive patients with chronic renal failure. The decrease of blood pressure lasted for approximately 3 h and maximum decrement was achieved in 1 h after oral administration of nifedipine (10 mg). Hypotensive action of the drug was associated with a constant decrease in total peripheral resistance and an increase in cardiac output, plasma renin activity (PRA), and plasma norepinephrine (noradrenaline). Initial PRA was apparently the major determinant of the rise in PRA since a close correlation was present between the initial value and the increase induced by nifedipine (r = 0.93, p less than 0.05). Marked reduction of blood pressure without noticeable side effects was observed in two cases who had not responded to previous antihypertensive treatment. These data suggest that nifedipine exerts its hypotensive action through peripheral vasodilation and may be an effective drug for treatment of hypertension during chronic renal failure.
Adolescent↗
Inotropic effects of vanadate in isolated rat and guinea-pig heart under conditions which modify calcium pools involved in contractile activation.
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Animals↗
Kinetics of appearance of differentiation-associated characteristics in ML-1, a line of human myeloblastic leukemia cells, after treatment with 12-O-tetradecanoylphorbol-13-acetate, dimethyl sulfoxide or 1-beta-D-arabinofuranosylcytosine.
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Cell Cycle↗
[Emission computed tomography using opposed dual cameras for 201Tl myocardial imaging: clinical usefulness of left ventricular axial tomography].
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Aortic Valve Insufficiency↗