Akira Takanaka

Showa Pharmaceutical University

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Kannosuke Fujimori

Pharmaceuticals and Medical Devices Agency

Yoshihito Omori

National Institute of Health Sciences

Kazuhide Inoue

Kyushu University

Ken Nakazawa

Saitama Medical University

Ryuichi Kato

Muroran Institute of Technology

S Nakaura

National Institute of Health Sciences

Momoko Sunouchi

National Institute of Health Sciences

Toru Kawanishi

Tokyo Institute of Technology

Kunio Kawashima

National Institute of Infectious Diseases

Satoru Tanaka

Japan Agency for Marine-Earth Science and Technology

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National Institute of Health Sciences

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National Institute of Health Sciences

Kyushu University

Osaka University

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Kyoto University

Keio University

Hokkaido University

Nihon University

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Selective and competitive antagonism by suramin of ATP‐stimulated catecholamine‐secretion from PC12 phaeochromocytoma cells

British Journal of Pharmacology (1991)

Kazuhide Inoue Ken Nakazawa Mica Ohara‐Imaizumi Tomoko Obama Kannosuke Fujimori

Suramin, a putative P 2 ‐antagonist, (10 to 300 μ m ) inhibited the adenosine 5′‐triphosphate (ATP)‐stimulated secretion of [ 3 H]‐noradrenaline or endogenous dopamine from phaeochromocytoma PC12 cells in a concentration‐dependent manner. Suramin (300 μ m ) did not affect the dopamine‐secretion stimulated by high K + or nicotine. Suramin shifted the concentration‐response curve for ATP to the right. The antagonism was competitive with a pA 2 value of 4.52. ATP also stimulated an increase in intracellular Ca 2+ concentration as determined by fura‐2 methods. Suramin antagonized this effect over the same concentration range that antagonized the ATP‐stimulated catecholamine secretion. These results suggest that suramin can be used as a selective and competitive antagonist of ATP in experiments concerning mechanisms of catecholamine‐secretion.

10.1111/j.1476-5381.1991.tb12216.x

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Citations (39)

EFFECT OF VITAMIN C DEFICIENCY ON THE METABOLISM OF DRUGS AND NADPH-LINKED ELECTRON TRANSPORT SYSTEM IN LIVER MICROSOMES

The Japanese Journal of Pharmacology (1969)

Ryuichi Kato Akira Takanaka Takao Oshima

Various drugs are inactivated by liver microsomes in the presence of NADPH and atomospheric oxygen (1). The enzymes catalyzing these reactions can activate molecular oxygen by a two-electron reduction so that one oxygen atom is introduced into the substrate leading to a hydroxylated product, whereas the second atom is reduced to water (1, 2). Recently the participation in these reactions of hemoprotein called cytochrome P-450 (3) as the oxygen-activating component (4-8) has been established (Fig. 1). The activity of drug-metabolizing enzymes of liver microsomes was altered by various factors, such as the administration of phenobarbital or methylcholanthrene (9, 10), thyroxine (11-13), anabolic hormone (11, 14, 15), carbon tetrachloride (11, 16) and morphine (11, 12), and adrenalectomy (11, 17), thyroidectomy (13), hepatectomy (18), starvation (19, 20), alloxan diabetes (11, 12) and low protein diet (16, 21, 22). It was also demonstrated that the activity of NADPH-linked electron transport system of liver microsomes was often altered in association with the alteration in the activity of drug-metabolizing enzymes under the above-given conditions (10, 13, 22, 26). Vitamin C is a well known component related to the control of oxido-reduction states of living cell, but detailed role of vitamin C has not been fully elucidated (27). On the other hand, Mitoma et al. (28), Tochino et al. (29) and more recently, Conney et al. (30) reported that the hydroxylation of acetanilide, hexobarbital and zoxazolamine was decreased in vitamin C deficient guinea-pigs. However, the studies on the mechanism of decreased hydroxylation activity in relation to the activity of NADPH-linked electron transport system has not yet been reported. The purpose of the present study, therefore, is to investigate whether or not the mechanism of decreased hydroxylation activity of liver microsomes from vitamin C deficient guinea-pigs is related to the decreased activity of NADPH-linked electron transport system.

Hexobarbital

10.1254/jjp.19.25

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Citations (48)

Oxysterols Inhibit Gap Junctional Communication between Rat Hepatocytes in Primary Culture

Pharmacology & Toxicology (1993)

Xinbiao Guo Yasuo Ohno Atsuko Miyajima Momoko Sunouchi Akira Takanaka

Several oxysterols were examined for their effect on gap junctional communication between rat hepatocytes in primary culture. 25-Hydroxycholesterol, 22(S)-hydroxycholesterol and 7 beta-hydroxycholesterol, in decreasing order of potency, markedly inhibited gap junctional communication. In contrast, 7-ketocholesterol showed no inhibitory effect. The inhibition of gap junctional communication by oxysterols was not a consequence of changes in cell viability, as measured by lactate dehydrogenase leakage and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity. The addition of exogenous cholesterol to the culture medium did not abolish the effect of 25-hydroxycholesterol, suggesting that the capacity of oxysterols to inhibit gap junctional communication is independent of their inhibitory effect on cholesterol synthesis. We suppose that inhibition of gap junctional communication may be an early sign of oxysterols-induced toxicity on hepatocytes.

Oxysterol

10.1111/j.1600-0773.1993.tb01949.x

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Comparative evaluation of different pathways for the liver toxicity of morphine using freshly isolated hepatocytes

Biochemical Pharmacology (1988)

Yasuo Ohno Kunisuke Nagamatsu Toru Kawanishi Hideharu Ikebuchi Takamichi Terao

Liver toxicity

10.1016/0006-2952(88)90052-4

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Citations (6)

Effects of Extract from a Herbal Drug, Cnidium Rhizome (Senkyu), on Contraction, Heart Rates and Membrane Potentials of Isolated Guinea Pig Atria

YAKUGAKU ZASSHI (1989)

Ken Nakazawa Kannosuke Fujimori Kazuhide Inoue Setsuko Sekita Akira Takanaka

Effects of extract from a herb, Cnidium rhizome (Senkyu), on isolated guinea pig atria were investigated pharmacologically and electrophysiologically. The methanol extract from Cnidium rhizome decreased the contraction and slightly increased the heart rates of the isolated atria. Extracts from five other herbs, such as Japanese anglica root (Toki), Peony root (Shakuyaku), Moutan bark (Botanpi), Glycyrrhiza (Kanzo), Bupleurum (Saiko), affected neither the contraction nor the heart rates. The methanol extract from Cnidium rhizome was fractionated with chloroform and water fractions. The chloroform fraction exerted potent negative inotropic and chronotropic effects in isolated atria. The contraction was attenuated by two major components in the chloroform fraction, ligustilide and senkyunolide, but the heart rates were scarecely affected by these components. The chloroform fraction induced changes in resting potentials and configurations of normal action potentials recorded in the isolated left atria : the resting potentials were depolarized, and the upstroke velocity of the action potentials decreased. Neither ligustilide nor senkyunolide exerted such effects. The upstroke velocity of action potentials recorded in partially depolarized atria was reduced by the chloroform fraction as well as ligustilide and senkyunolide. The mechanisms underlying the effects of the extract from Cnidium rhizome were discussed.

Bupleurum

Glycyrrhiza

Atrium (architecture)

10.1248/yakushi1947.109.9_662

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Citations (9)

[Effects of triclosan on fetal developments of rats].

PubMed (1987)

K Kawashima S Nakaura Motoko Yamaguchi Satoru Tanaka Akira Takanaka

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