Effect of Compounds Affecting the Adrenergic Mechanism on Cell Growth and Division of Tetrahymena Pyriformis W

Abstract

Janakidevi et al. (1) showed that the ciliated protozoan, Tetrahymena pyriformis, could biosynthesize both of adrenaline and noradrenaline, while the flagellated protozoan, Crithidia fasciculata, biosynthesized only adrenaline. Accordingly, Blum et al. (2) studied the effect of reserpine on the protozoan and found that it inhibited growth and decreased the catecholamine content. Furthermore, Blum (3) investigated the effects of drugs which interacted with the action of catecholamine in mammals, on the glycogen content and growth of Tetrahymena, and suggested a relationship between glycogen synthesis and the control system for adrenergic metabolism in Tetrahymena.Later, serotonin was also discovered in both Crithidia and Tetrahymena by Janakidevi et al. (4). Furthermore, Blum et al. (5) suggested that clofibrate, a hypolipidemic agent, inhibited glyconeogenesis or activated glycogenolysis in Tetrahymena. And recently, Blum (6) reported that adrenergic control system of Tetrahymena influenced a peroxisomal enzyme which acted the first step of glyconeogenesis from acetyl-CoA.In an earlier publication from our laboratory (7), we recognized that the growth of Tetrahymena was promoted by dibenamine or ergotamine. The present paper is on the effect of the compounds used in previous experiments, on growth during 72 hours, and on the cell growth and division in one life cycle of the protozoan. MATERIALS AND METHODS Culture method of Tetrahymena for 72 hoursTetrahymena pyriformis W was cultured in a medium composed of 2% polypepton and 0.1 % yeast extract at pH 7.2, 26°C, for 72 hours after addition of the drugs. All procedures were carried out aseptically. The growth was estimated with a photocolorimeter (Spec tronic 20, Shimadzu Seisakusho, Kyoto) at 650 m,u and the cells were counted in a Coulter counter (Model B, Coulter Co., Hialeath) which was set at an aperture current-' of 8 and amplification-' of 2.2. Experiment on the cell size distribution for one life cycle Tetrahymena was cultured in the medium for 5 days at 26°C, prior to the following experiments. The size distribution of the protozoan in which one life cycle normally took

Adrenergic Mechanism in Tetrahymena Iii Cyclic Adenosine 3', 5'-Monophosphate and Cell Proliferation

“…Recently, Rosensweig et al (6) ob served the presence of adenyl cyclase activity in Tetrahyntena as well as the activation of this enzyme by adrenaline and serotonin, and suggested that the stimulation of adenyl cyclase by drugs was mediated through a i3-type adrenergic receptor. This hypothesis appears to be related to our previous observations (13,14) that low concentrations of n adrenergic blockers promote growth of the protozoan while 13-blockers inhibit it. As shown in Table I, the level of cAMP in Tetrahyinena varied inversely with the rate of cell proliferation.…”

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

“…Barka subsequently confirmed that isoproterenol increased the rate of mitosis and triggered DNA synthesis [96]. The converse, a reduction of proliferation due to PRO was also reported in the same era, for example Iwata, Kariya and Fujimoto showed that in a ciliated protozoan beta-adrenergic blockade, with PRO and other agents, was associated with a reduced rate of growth [97]. It has since been shown that PRO is able to inhibit the increase in cancer cell proliferation associated with catecholamines or isoproterenol in a number of cancer cell types [56, 98–100].…”