The inhibition of tryptophan hydroxylase, not protein synthesis, reduces the brain trapping of alpha-methyl-L-tryptophan: an autoradiographic study.
The effects of the tryptophan hydroxylase (TPH) inhibitor p-chlorophenylalanine (PCPA; 200mg/kg; 3 days), and of the protein synthesis inhibitor cycloheximide (CXM, 2mg/kg), on regional serotonin (5-HT) synthesis were studied using the alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) autoradiographic method. The objectives of these investigations were to evaluate the changes, if any, on 5-HT synthesis, as measured with alpha-MTrp method, following the inhibition of TPH by PCPA, or the inhibition of proteins synthesis by CXM. The rats were used in the tracer experiment approximately 24h after the last dose of PCPA was administered, and in the CXM experiments, they were used 30 min following a single injection of CXM. In both experiments, the control rats were injected with the same volume of saline (0.5 ml/kg; s.c.) and at the same times as the drug injections. The results demonstrate that trapping of alpha-MTrp, which is taken to be related to brain 5-HT synthesis, is drastically reduced (40-80%) following PCPA treatment. The inhibition of protein synthesis with CXM did not have a significant effect on the global brain trapping of alpha-MTrp and 5-HT synthesis. These findings suggest that the brain trapping of alpha-[14C]MTrp relates to brain 5-HT synthesis, but not to brain protein synthesis.
Tohyama
Yoshihiro
Y
Cone Laboratory for Neurosurgical Research, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Que., Canada H3A 2B4.
Takahashi
Sho
S
Merid
Maraki Fikre
MF
Watanabe
Arata
A
Diksic
Mirko
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan; D003513:Cycloheximide; D014365:Tryptophan Hydroxylase; D010134:Fenclonine