Aroclor 1254 inhibits tryptophan hydroxylase activity in rat brain.
Previous studies have shown that oral exposure of rats to polychlorinated biphenyls (PCBs) results in reduced 5-hydroxytryptamine (5-HT) concentrations in certain brain regions. In the present study, we investigated whether the PCB mixture Aroclor 1254 (0.33 mg/g body weight as a single oral dose) can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis, and reduce 5-HT concentrations in selected brain areas. In two separate experiments, Aroclor 1254 exposure consistently reduced TPH activity in the brainstem (7.2 and 8.7%), frontal cortex (17.4 and 14.8%), and hypothalamus (10.7 and 9.4%) without altering the rats' food intake or growth. Moreover, Aroclor 1254 accumulation in the frontal cortex demonstrated a negative correlation with TPH activity (correlation coefficient -0.82). In addition, 5-HT concentrations decreased in the brainstem and frontal cortex after Aroclor 1254 exposure by 9.1 and 19.7%, respectively. These results suggest that the Aroclor 1254-induced decreases in 5-HT concentrations in certain areas of the rat brain are due to inhibition of TPH activity, similar to our recent observations in Atlantic croaker, and that TPH is one of the targets of PCB neurotoxicity in both fish and mammals.
Khan
Izhar A
IA
Marine Science Institute, The University of Texas at Austin, 750 Channelview Drive, Port Aransas, TX 78373, USA. ikhan@utmsi.utexs.edu
Thomas
Peter
P
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000633:toxicity; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*
D004785:Environmental Pollutants; D012702:Serotonin Antagonists; D020111:Chlorodiphenyl (54% Chlorine); D012701:Serotonin; D014365:Tryptophan Hydroxylase