PMID- 1969761
OWN - NLM
STAT- MEDLINE
DCOM- 19900521
LR  - 20190613
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 510
IP  - 1
DP  - 1990 Feb 26
TI  - MDMA (ecstasy) effects on cultured serotonergic neurons: evidence for 
      Ca2(+)-dependent toxicity linked to release.
PG  - 97-103
AB  - Animal studies have established a correlation between release of 
      5-hydroxytryptamine (5-HT) and the long-term reduction of 5-HT (toxicity) by 
      3,4-methylenedioxymethamphetamine (MDMA) with the S(+) enantiomer being more 
      active than the R(-). Using a microculture system of fetal raphe neurons, the 
      enantiomers of MDMA were tested to determine if a similar difference in potency 
      existed. The results showed that the development of the uptake capacity of 
      [3H]5-HT in 4-day cultures was half-maximally inhibited by a single application 
      at time of plating of 5 X 10(-6) M S(+)-MDMA and 5 X 10(-5) M R(-)-MDMA. In order 
      to determine if the Ca2(+)-independent release (chemically induced through the 
      transporter protein and inhibited by reuptake blockers) or the Ca2(+)-dependent 
      release (K(+)-induced and inhibited by presynaptic receptors) contributed to the 
      toxicity, fluoxetine and D1 and alpha 2 agonists were studied. The results showed 
      that both forms of release were involved in the loss of [3H]5-HT uptake capacity, 
      with the direct MDMA-induced Ca2(+)-independent (fluoxetine-sensitive) release 
      being the first step. Evidence from binding studies indicates that MDMA has a 
      micromolar affinity for the 5-HT2 receptor, and our studies in culture showed 
      that ketanserin, a specific 5-HT2 antagonist, was effective at attenuating the 
      effects of S(+)-MDMA on the development of the [3H]5-HT uptake capacity by the 
      cultured raphe neurons. The 5-HT2 receptor is linked to increased intracellular 
      Ca2+ through a second messenger phosphatidylinositol (PI)-hydrolysis 
      mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Azmitia, E C
AU  - Azmitia EC
AD  - Department of Biology, New York University, NY 10003.
FAU - Murphy, R B
AU  - Murphy RB
FAU - Whitaker-Azmitia, P M
AU  - Whitaker-Azmitia PM
LA  - eng
GR  - 271-87-8144/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amphetamines)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 97F9DE4CT4 (Ketanserin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Calcium/*physiology
MH  - Cells, Cultured
MH  - Embryo, Mammalian
MH  - Fluoxetine/pharmacology
MH  - Ketanserin/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Raphe Nuclei/*cytology/drug effects/metabolism
MH  - Rats
MH  - Serotonin/*metabolism
EDAT- 1990/02/26 00:00
MHDA- 1990/02/26 00:01
CRDT- 1990/02/26 00:00
PHST- 1990/02/26 00:00 [pubmed]
PHST- 1990/02/26 00:01 [medline]
PHST- 1990/02/26 00:00 [entrez]
AID - 0006-8993(90)90732-Q [pii]
AID - 10.1016/0006-8993(90)90732-q [doi]
PST - ppublish
SO  - Brain Res. 1990 Feb 26;510(1):97-103. doi: 10.1016/0006-8993(90)90732-q.