PMID- 9283711
OWN - NLM
STAT- MEDLINE
DCOM- 19980105
LR  - 20181201
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 121
IP  - 8
DP  - 1997 Aug
TI  - Carrier-dependent and Ca(2+)-dependent 5-HT and dopamine release induced by 
      (+)-amphetamine, 3,4-methylendioxymethamphetamine, p-chloroamphetamine and 
      (+)-fenfluramine.
PG  - 1735-43
AB  - 1. The mechanism underlying 5-hydroxytryptamine (5-HT) and/or dopamine release 
      induced by (+)-amphetamine ((+)-Amph), 3,4-methylendioxymethamphetamine (MDMA), 
      p-chloroamphetamine (pCA) and (+)-fenfluramine ((+)-Fen) was investigated in rat 
      brain superfused synaptosomes preloaded with the 3H neurotransmitters. 2. Their 
      rank order of potency for [3H]-5-HT-releasing activity was the same as for 
      inhibition of 5-HT uptake (pCA > or = MDMA > or = (+)-Fen > > (+)-Amph). 
      Similarly, their rank order as [3H]-dopamine releasers and dopamine uptake 
      inhibitors was the same ((+)-Amph > > pCA = MDMA > > (+)-Fen). We also confirmed 
      that the release induced by these compounds was prevented by selective 
      transporter inhibitors (indalpine or nomifensine). 3. [3H]-5HT and/or 
      [3H]-dopamine release induced by all these compounds was partially (31-80%), but 
      significantly Ca(2+)-dependent. Lack of extracellular Ca2+ did not alter uptake 
      mechanisms nor did it modify the carrier-dependent dopamine-induced [3H]-dopamine 
      release. (+)-Amph-induced [3H]-dopamine release and pCA- and MDMA-induced 
      [3H]-5-HT release were significantly inhibited by omega-agatoxin-IVA, a specific 
      blocker of P-type voltage-operated Ca(2+)-channels, similar to the previous 
      results on (+)-Fen-induced [3H]-5-HT release. 4. Methiothepin inhibited the 
      Ca(2+)-dependent component of (+)-Amph-induced [3H]-dopamine release with high 
      potency (70 nM), as previously found with (+)-Fen-induced [3H]-5-HT release. The 
      inhibitory effect of methiothepin was not due to its effects as a transporter 
      inhibitor or Ca(2+)-channel blocker and is unlikely to be due to its antagonist 
      properties on 5-HT1/2, dopamine or any other extracellular receptor. 5. These 
      results indicate that the release induced by these compounds is both 
      'carrier-mediated' and Ca(2+)-dependent (possibly exocytotic-like), with the 
      specific carrier allowing the amphetamines to enter the synaptosome. The 
      Ca(2+)-dependent release is mediated by Ca(2+)-influx (mainly through P-type 
      Ca(2+)-channels), possibly triggered by the drug interacting with an unknown 
      intracellular target, affected by methiothepin, common to both 5-HT and dopamine 
      synaptosomes.
FAU - Crespi, D
AU  - Crespi D
AD  - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
FAU - Mennini, T
AU  - Mennini T
FAU - Gobbi, M
AU  - Gobbi M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Carrier Proteins)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 2DS058H2CF (Fenfluramine)
RN  - 333DO1RDJY (Serotonin)
RN  - 55D94103HL (Methiothepin)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - CK833KGX7E (Amphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - SY7Q814VUP (Calcium)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Amphetamine/*pharmacology
MH  - Animals
MH  - Calcium/*physiology
MH  - Carrier Proteins/*physiology
MH  - Dopamine/*metabolism
MH  - Fenfluramine/*pharmacology
MH  - Male
MH  - Methiothepin/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neurotransmitter Uptake Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - p-Chloroamphetamine/pharmacology
PMC - PMC1564879
EDAT- 1997/08/01 00:00
MHDA- 1997/08/01 00:01
PMCR- 1998/08/01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/08/01 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
PHST- 1998/08/01 00:00 [pmc-release]
AID - 0701325 [pii]
AID - 10.1038/sj.bjp.0701325 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1997 Aug;121(8):1735-43. doi: 10.1038/sj.bjp.0701325.