Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by sigma2 receptor agonists and antagonists.
Some sigma receptor ligands have been shown to bind with low affinity to the dopamine transporter and to inhibit [3H]dopamine uptake. It has not previously been shown whether any of these compounds influence release of dopamine via facilitated exchange diffusion. To further examine the nature of the interaction between sigma receptor ligands and the dopamine transporter, the effects of sigma receptor ligands on amphetamine-stimulated [3H]dopamine release were examined in slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both (+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated [3H]dopamine release at concentrations consistent with their affinities for sigma2 receptors. In contrast, BD737 (1S.2R-(-)-cis-N-¿2-(3,4-dichlorophenyl)ethyl¿-N-methyl-2-(1-pyrrolidiny l)cyclohexylamine), a sigma1 receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer of pentazocine alone had any effect on basal [3H]dopamine release under these conditions. Three antagonists at sigma receptors, one of which is non-selective for subtypes, and two of which are sigma2-selective, all blocked the enhancement of stimulated release produced by (+)-pentazocine. Enhancement of stimulated release by (-)-pentazocine was similarly blocked by sigma2 receptor antagonists. Our data support the contention that it is possible to regulate transporter-mediated events with drugs that act at a subpopulation of sigma receptors pharmacologically identified as the sigma2 subtype.
Izenwasser
S
S
Psychobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Thompson-Montgomery
D
D
Deben
S E
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Chowdhury
I N
IN
Werling
L L
LL
D000661:Amphetamine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D003514:Cyclohexylamines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009294:Narcotics / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D010423:Pentazocine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017480:Receptors, sigma / Q000819:agonists* / Q000037:antagonists & inhibitors*
D000700:Analgesics; D002352:Carrier Proteins; D003514:Cyclohexylamines; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009294:Narcotics; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; C075567:BD 737; D000661:Amphetamine; D008274:Magnesium; D010423:Pentazocine; D002118:Calcium; D004298:Dopamine