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Biomedical subjects

A Kishimoto

Publications and source records attributed to A Kishimoto.

At least 109 records · Page 6Linked to original sources
PubMed1983

Proteolytic activation of calcium-activated, phospholipid-dependent protein kinase by calcium-dependent neutral protease.

A Ca2+-dependent protease I), which hydrolyzes casein at Ca2+ concentrations lower than the 10(-5) M range, is purified roughly 4000-fold from the soluble fraction of rat brain. This protease is able to activate Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) by limited proteolysis analogously to the previously known Ca2+-dependent analogously to the previously known Ca2+-dependent protease (Ca2+ protease II) which is active at the millimolar range of Ca2+ (Inoue, M., Kishimoto, A., Takai, Y., and Nishizuka, Y. (1977) J. Biol. Chem. 252, 7610-7616). The protein kinase fragment thus produced shows a molecular weight of about 5.1 X 10(4), and is significantly smaller than native protein kinase C (Mr = 7.7 X 10(4). Although protein kinase C may be normally activated in a reversible manner by the simultaneous presence of phospholipid and diacylglycerol at Ca2+ concentrations less than 10(-6) M, this enzyme fragment is fully active without any lipid fractions and independent of Ca2+. The limited proteolysis of protein kinase C is markedly enhanced in the velocity by the addition of phospholipid and diacylglycerol, which are both required for the reversible activation of the enzyme. However, casein hydrolysis by this protease is not affected by phospholipid and diacylglycerol. Available evidence suggests that, at lower concentrations of this divalent cation, Ca2+ protease I reacts preferentially with the active form of protein kinase C which is associated with membrane, and converts it to the permanently active form. In contrast, the inactive form of protein kinase C, which is free of membrane phospholipid, does not appear to be very susceptible to the proteolytic attack. It remains unknown, however, whether this mechanism of irreversible activation of protein kinase C does operate in physiological processes. It is noted that Ca2+ protease II, which is active at higher concentrations of Ca2+, proteolytically activates protein kinase C irrespective of the presence and absence of phospholipid and diacylglycerol.

Animals↗
PubMed1983

Age differences in effects on blood pressure, flicker fusion frequency, salivation and pharmacokinetics of single oral doses of dothiepin and amitriptyline.

Blood pressure, critical flicker fusion frequency (CFF), salivary flow rate and pharmacokinetics were compared in 7 young healthy volunteers (average age: 22.7 years) and in 7 elderly healthy volunteers (average age: 70.6 years) after single oral doses of the antidepressants dothiepin (DP) 25 mg and amitriptyline (AMP) 25 mg. Systolic blood pressure fell further and the reduction lasted longer in the elderly than in the young after both drugs. The decrease in CFF after AMP 25 mg, and the reduction in salivary flow rate after either DP 25 mg or AMP 25 mg were larger in the elderly than in the young. Plasma levels, T1/2 and Cl of both drugs in the elderly were also higher, longer and smaller, respectively, in the elderly. Clearance was found to be reduced in the elderly. More cautions dosage regimens of these drug should be considered for elderly patients.

Adult↗
PubMed1983

Influence of single doses of dothiepin and amitriptyline on physiological measures and psychomotor performance in normal young and elderly volunteers.

The subjects were 14 (7 young and 7 elderly) men. Self-rating, and physiological and psychological measurements were applied, and experiments were performed 24 h after drug administrations. 25 mg dothiepin hydrochloride (DP) decreased critical flicker frequency less than 25 mg AMP in both age groups. 25 mg DP reduced whole mouth salivary rates less than 25 mg AMP, especially in the young subjects. 25 mg DP decreased diastolic blood pressure more than 25 mg AMP. Systolic blood pressure (after 25 mg DP and 25 mg AMP) and whole mouth salivary rates (after 25 mg AMP) were affected more intensely in the elderly than in the young volunteers.

Adult↗
PubMed1983

Long-term prophylactic effects of carbamazepine in affective disorder.

The prophylactic effects of carbamazepine (CBZP) were studied in 32 patients with affective disorder who were receiving long-term therapy with CBZP. Complete inhibition of both manic and depressive episodes was observed in four cases, reduced incidence of episodes or decreased intensity of symptoms in twenty, and no change in eight. CBZP was significantly more effective in cases with an onset before the age of 20, and subjects showing a continuous pattern of alternating episodes responded better than those with a more intermittent history of mania and depression. Where CBZP had an effect it was generally apparent soon after therapy started. These results suggest that in some cases CBZP is an agent suitable for long-term continuous prophylactic therapy in manic-depressive disorder.

Adult↗
PubMed1981

Calcium-dependent neural proteases, widespread occurrence of a species of protease active at lower concentrations of calcium.

A species of neutral protease having high affinity for Ca2+ in the 10(-5) M range, originally found in canine cardiac muscle (Mellgren, R.L. (1980) FEBS Lett. 109, 129-133), is detected in a wide variety of rat tissues when a sensitive assay with 125I-iodinated casein as substrate is employed. This species of protease absolutely requires Ca2+, and other divalent cations are practically inactive. Although the activity of this enzyme apparently shows striking diversity among tissues tested, the enzymes obtained from various sources reveal similar physical and kinetic properties, and are capable of activating as Ca2+-activated, phospholipid-dependent protein kinase by limited proteolysis. The enzyme has a pH optimum at 7.5 to 8.0 and a molecular weight of about 8.8 X 10(4). The enzyme in its purified form is very sensitive to leupeptin and other thiol-protease inhibitors, but that in crude preparations is far less susceptible to the same inhibitors.

Animals↗
PubMed1981

A new possible regulatory system for protein phosphorylation in human peripheral lymphocytes. II. Possible relation to phosphatidylinositol turnover induced by mitogens.

Ca++-activated, phospholipid-dependent protein kinase present in human peripheral lymphocytes requires a small amount of diacylglycerol in addition to phospholipid, particularly at lower concentrations of Ca++. It is necessary that such diacylglycerol contain unsaturated fatty acid at least at position 2. Saturated diacylglycerols such as dipalmitin and distearin are far less effective. Kinetic analysis indicates that unsaturated diacylglycerol greatly increases the apparent affinity of the enzyme for phospholipid, and sharply decreases the Ca++ concentration to the micromolar range that gives rise to the maximum enzyme activation. Among various phospholipids tested, phosphatidylserine is most active in supporting enzymatic activity. Phosphatidylinositol and phosphatidylethanolamine are less effective. Phosphatidylcholine, phosphatidic acid, sphingomyelin, and lysophosphatidylcholine are inert. It is most likely, therefore, that various lymphocyte mitogens induce specific hydrolysis of phosphatidylinositol to produce such an active unsaturated diacylglycerol, which in turn serves as a second messenger for the selective activation of this unique protein kinase. Dibucaine and chlorpromazine appear to interact with phospholipid and thereby inhibit the activation process of this enzyme. Cyclic nucleotide-dependent protein kinases are not susceptible to these phospholipid-interacting drugs.

Chlorpromazine↗
PubMed1980

Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover.

Ca2+-activated, phospholipid-dependent protein kinase from various mammalian tissues (Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T., and Nishizuka, Y (1979) J. Biol. Chem. 254, 3692-3695) was greatly stimulated by the addition of diacylglycerol at less than 5% (w/w) the concentration of phospholipid. This stimulation was due to an increase in the apparent affinity of enzyme for phospholipid and to a concomitant decrease in the Ka value for Ca2+ from about 1 x 10(-4) M to the micromolar range. Diacylglycerol alone showed little or no effect on enzymatic activity over a wide range of Ca2+ concentrations. This effect was greatest for diacylglycerol which contained unsaturated fatty acid at least at position 2. The active diacylglycerols so far tested included diolein, dilinolein, diarachidonin, 1-stearoyl-2-oleoyl diglyceride, and 1-stearoyl-2-linoleoyl diglyceride. In contrast, diacylglycerols containing saturated fatty acids such as dipalmitin and distearin were far less effective. Triacyl- and monoacylglycerols were totally ineffective, irrespective of the fatty acyl moieties. Cholesterol and free fatty acids were also ineffective. Based on these observations, a possible coupling is proposed between the protein kinase activation and phosphatidylinositol turnover which can be provoked by various extracellular messengers.

Animals↗
PubMed1980

Dynamic properties of concentrated suspensions of charged polystyrene spheres.

Ordered structure formation of charged polystyrene spheres was studied by measuring the order-disorder phase diagrams as well as the mechanical properties. The phase diagrams indicate that the ordering of polystyrene spheres obeys Lindemann's law of crystal melting, in which the Lindemann's parameter is about 5%. The rigidity of about 10(3) dyn/cm(2) was observed in the ordered suspension of polystyrene spheres as measured by a torsional quartz crystal method. The steady flow properties of suspensions of polystyrene spheres showed a remarkable change from a Bingham body to a Newtonian liquid at the transition point. The limit of elasticity in the ordered phase was about 1 dyn/cm(2). The viscosity in the disordered phase was well explained by the free volume theory of liquids. It is concluded from these facts that the ordered phase of polystyrene spheres is a real "crystal" whereas the disordered phase is a "liquid". Properties of ordered structures in biological systems are also discussed.

Journal Article↗
PubMed1979

Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids.

The proenzyme of a Ca2+-dependent protease-activated protein kinase previously obtained from mammalian tissues (Inoue, M., Kishimoto, A., Takai, Y., and Nishizuka, Y. (1977) J. Biol. Chem. 252, 7610-7616) was enzymatically fully active without limited proteolysis when Ca2+ and a membrane-associated factor were simultaneously present in the reaction mixture. The activation process was reversed by removing Ca2+ with ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid. An apparent Ka value for Ca2+ was less than 5 x 10(-5) M. Other divalent cations were inactive except for Sr2+, which was 5% as active as Ca2+. The factor was almost exclusively localized in membrane fractions of various tissues including brain, liver, kidney, skeletal muscle, blood cells, and adipose tissue. It was easily extractable with chloroform/methanol (2:1), and was recovered in the phospholipid fraction. In fact, this membrane factor could be replaced by chromatographically pure phosphatidylinositol, phosphatidylserine, phosphatidic acid, or diphosphatidylglycerol. Phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin were far less effective under the comparable conditions. Ca2+-dependent modulator protein was unable to support enzymatic activity. The enzyme thus activated showed an ability to phosphorylate five histone fractions and muscle phosphorylase kinase, and appeared to possess multifunctional catalytic activities.

Animals↗