Effects of Phenothiazines on Growth, Glucose Uptake, and Cell Composition in Tetrahymena Pyriformis W

Abstract

The effect of phenothiazine derivatives on growth, glucose uptake, and cell composition was studied in the ciliate protozoan Tetrahymena pyriformis W. The most effective inhibitor of growth in a chemically defined medium was promazine (PRZ), followed by chlorpromazine (CPZ), promethazine (PMZ), prochlorperazine (PCP), acetophenazine (ACP), and trifluoperazine (TFP). The uptake of glucose was highest in resting suspensions of cells in the logarithmic phase (40 hours), but decreased with increasing age of the culture. Little or no uptake of glucose occurred in cells pre-inhibited by PRZ or CPZ. The most effective inhibitor of glucose uptake was TFP, followed by ACP, PCP, PRZ, CPZ, and PMZ. The concentration of protein in cells grown with Tween 80 was unaffected by PRZ, although total cell populations were reduced. Under these conditions, PRZ or CPZ delayed the accumulation of lipid in the cells. Similarly, PRZ reduced the amount of RNA and DNA during the logarithmic phase.These results demonstrated that phenothiazine derivatives can influence lipid and nucleic acid levels in Tetrahymena, and further suggest that the drugs may interfere directly with the mechanism of glucose transport into the cell. These observations support the hypothesis that metabolic effects are related to the ability of phenothiazine derivatives to alter permeability of cell membranes.

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

“…Cell growth was inhibited by chlorpromazine which is an a-blocker. Rogers (8) showed that phenothiazine derivatives altered the membrane permeability of Tetrahymena. So, the inhibition of cell growth by chlorpromazine could be due to its direct action on membrane permeability of Tetrahymena and not be related to its a-adrenergic blocking activity.…”

Cytological Effects of Phenothiazine Tranquilizing Agents on Barley Meristems

“…Several authors have noted a reduced growth and inhibited mitosis and/or DNA syn thesis (4, 5, 8,15). These tranquilizing agents have also resulted in chromosomal damage (11,14), altered membrane permeability (2, 9) and a reduction in cellular respiration (3, 12).…”

Equine laminitis: a tissue microdialysis study of lamellar bioenergetics

“…This mechanism is supported by the increase in pyruvate and decrease in L:P in lamellar dialysate after ACP administration, a pattern consistent with increased uptake and metabolism of glucose rather than decreased supply (Zhang and Natowicz, 2013). However, phenothiazine derivatives such as ACP have been shown to induce a decrease in glucose uptake as a result of alteration in cell membrane permeability (Rogers, 1966) in other tissues including rat diaphragm and spinal cord , and even in Protozoa (Rogers, 1966). This effect was not apparent in lamellar tissue, which could be also due to the unique feature of a high number of AVA in this tissue .…”

“…Phenothiazine derivatives have been shown to have direct effects on glucose uptake in vitro, but in the published studies they actually caused reduced cellular glucose uptake in mammalian tissues [42] and protozoa [43]. In the horse digit ACP, through its α-adrenergic inhibitory effects [44], is likely to cause opening of arterio-venous anastomoses (AVAs), richly present in lamellar tissue [18; 38; 45] but not necessarily the skin over the tail.…”

“…This effect was not apparent in lamellar tissue, which could be also due to the unique feature of a high number of AVA in this tissue . Thus, changes in metabolic rate, modulated by the thermoregulatory effects of AVA, may override the decrease in glucose uptake observed in other tissues in response to phenothiazine derivatives Rogers, 1966), and may have a profound influence on lamellar energy metabolism and this requires further study.…”