Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells

doi:10.1016/S0278-5846(98)00092-X

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 23, Issue 1, January 1999, Pages 69-80

https://doi.org/10.1016/S0278-5846(98)00092-X Get rights and content

Abstract

1.
1. Adherence of the PC12 cell line to poly-l-lysine (PLL) on tissue culture dishes stimulated glucose transport into the cells. Fluphenazine, chlorpromazine, clozapine and haloperidol inhibited glucose uptake in this system after a short (30 min) preincubation with drug. The IC₅₀'s for this effect were typically in the range of 5–40 μM.
2.
2. Following longer exposures to the drugs (24 hr), there was a significant increase (~ 3-fold) in the cellular levels of the glucose transporter (GLUT) isoforms, GLUT1 and GLUT3.
3.
3. Long-term incubation (48 hr), especially with the phenothiazine drugs, was accompanied by a marked reduction in cell growth and proliferation. The rank ordering of the potencies of the drugs was essentially the same for these various effects: fluphenazine > chlorpromazine > clozapine ≈ haloperidol.
4.
4. It is suggested that the effects on glucose transport reported here may complicate the interpretation of positron emission tomography (PET) studies that rely on the uptake of radiolabeled glucose analogs to measure the physiological response to these drugs.

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Experimental laboratory studyAntipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells

Abstract

Phenothiazine derivatives and glucose metabolism

J. Neuropsychiatry

Effects of psychotropic drugs on the erythrocyte permeability to glucose and ethylidene glucose

Biochem. Pharmacol.

Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects

Am. J. Psychiatry

Interleukin-3 facilitates glucose transport in a myeloid cell line by regulating the affinity of the glucose transporter for glucose: involvement of protein phosphorylation in transporter activation

Biochem. J.

The role of membrane transport in the control of glucose metabolism and its coupling to cellular function

Can. J. Physiol. Pharmacol.

The brain metabolic patterns of clozapine- and fluphenazine-treated patients with schizophrenia during a continuous performance task.

Arch. Gen. Psychiatry

Neuronal differentiation in PC12 cells is accompanied by diminished inducibility of Hsp70 and Hsp60 in response to heat and ethanol

Neurochem. Res.

Attachment of PC12 cells to adhesion substratum induces the accumulation of glucose transporters (GLUTs) and stimulates glucose metabolism

Neurochem. Res.

Influence of various substances which induce and inhibit aggregation on the uptake of deoxyglucose by human blood platelets

J. Pharmacol. Exp. Ther.

The phenothiazine tranquilizers: Biochemical and biophysical actions

Int. Rev. Neurobiol.

Hyperglycemia and glycosuria following chlorpromazine therapy

J. Amer. Med. Assoc.

Dopamine receptor agonists and antagonists enhance ATP-activated currents

Eur. J. Pharmacol.

Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells

Eur. J. Pharmacol.

Use of CellTiter 96 reagents in a semi-automatic assay of neuronal survival

Neural Notes

Evidence for a family of transporter-like proteins. Sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues

J. Biol. Chem.

The general metabolism of the brain in vivo

Regulation of the expression of glucose transporters by glucose: a review of studies in vivo and in cell culture

FASEB J.

Diabetic ketoacidosis associated with clozapine treatment

Am. J. Psychiatry

Experimental laboratory study
Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells

Inhibition by antipsychotic drugs of L-type Ca²⁺ channel current in PC12 cells