PMID- 8496826
OWN - NLM
STAT- MEDLINE
DCOM- 19930622
LR  - 20141120
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 265
IP  - 2
DP  - 1993 May
TI  - Short-term effects of 2,4,5-trihydroxyamphetamine, 
      2,4,5-trihydroxymethamphetamine and 3,4-dihydroxymethamphetamine on central 
      tryptophan hydroxylase activity.
PG  - 813-8
AB  - In previous studies, we have reported the long-term effects of several 
      metabolites of 3,4-methylenedioxymethamphetamine (MDMA) on tryptophan hydroxylase 
      (TPH) activity. In this study, the short-term effects of three metabolites of 
      MDMA. 2,4,5-trihydroxyamphetamine (THA), 2,4,5-trihydroxymethamphetamine (THM) 
      and 3,4-dihydroxymethamphetamine, and the in vitro effect of THA on TPH activity 
      are reported. After short-term treatment, hippocampal TPH activity was decreased 
      to 8 and 54% of control in response to THA and THM, respectively, but was 
      unaltered after 3,4-dihydroxymethamphetamine. Incubating TPH from THM-treated 
      rats with dithiothreitol under nitrogen failed to reverse the decrease in enzyme 
      activity induced by THM treatment. THA also decreased tyrosine hydroxylase 
      activity to 75% of control, whereas the enzyme activity remained unaltered by 
      THM. The structural analog of THA, 6-hydroxydopamine, failed to reproduce the 
      effect of THA on TPH activity; however, 5,6-dihydroxytryptamine decreased 
      hippocampal TPH activity to 18% of control. In the in vitro study, the 
      hippocampus and the striatum were incubated in varying concentrations of THA. 
      After a 1-h incubation at 37 degrees C, hippocampal TPH activity was decreased to 
      83, 71, 68, 47 and 3% of control after exposure to 0.001, 0.01, 0.1, 0.5 or 5.0 
      mM THA, respectively; striatal TPH activity was reduced to 98, 95, 70, 54 and 17% 
      of control, respectively. Incubating the enzyme under reducing conditions failed 
      to restore the enzyme activity to control levels.(ABSTRACT TRUNCATED AT 250 
      WORDS)
FAU - Elayan, I
AU  - Elayan I
AD  - Department of Pharmacology and Toxicology, University of Utah, Salt Lake City.
FAU - Gibb, J W
AU  - Gibb JW
FAU - Hanson, G R
AU  - Hanson GR
FAU - Lim, H K
AU  - Lim HK
FAU - Foltz, R L
AU  - Foltz RL
FAU - Johnson, M
AU  - Johnson M
LA  - eng
GR  - DA 00869/DA/NIDA NIH HHS/United States
GR  - DA 04222/DA/NIDA NIH HHS/United States
GR  - DA 05860/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Amphetamines)
RN  - 136706-32-6 (2,4,5-trihydroxymethamphetamine)
RN  - 136706-33-7 (2,4,5-trihydroxyamphetamine)
RN  - 15398-87-5 (alpha-methylepinine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - R7339QLN1C (Deoxyepinephrine)
RN  - W2QY253O8S (5,6-Dihydroxytryptamine)
SB  - IM
MH  - 5,6-Dihydroxytryptamine/pharmacology
MH  - Amphetamines/pharmacology
MH  - Animals
MH  - Corpus Striatum/*drug effects/enzymology
MH  - Deoxyepinephrine/*analogs & derivatives/pharmacology
MH  - Enzyme Activation
MH  - Hippocampus/*drug effects/enzymology
MH  - In Vitro Techniques
MH  - Male
MH  - Methamphetamine/*analogs & derivatives/pharmacology
MH  - Oxidopamine/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tryptophan Hydroxylase/*metabolism
EDAT- 1993/05/01 00:00
MHDA- 1993/05/01 00:01
CRDT- 1993/05/01 00:00
PHST- 1993/05/01 00:00 [pubmed]
PHST- 1993/05/01 00:01 [medline]
PHST- 1993/05/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1993 May;265(2):813-8.