Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells.
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 microM. 2. Following longer exposures of the drugs (24 hr), there was a significant increase (approximately 3-fold) in the cellular levels of the glucose transporter (GLUT) isoforms, GLUT1 and GLUT3. 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 approximately haloperidol. 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.
Dwyer
D S
DS
Department of Psychiatry, LSU Medical Center-Shreveport Shreveport, USA. ddwyer@lsumc.edu
Pinkofsky
H B
HB
Liu
Y
Y
Bradley
R J
RJ
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D005947:Glucose