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Acceleration of serotonin transporter transport-associated current by 3,4-methylenedioxymethamphetamine (MDMA) under acidic conditions.
Neurosci Lett. 2007 Nov 27; 428(2-3):72-6.NL

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) selectively releases serotonin (5-HT) from neurons after uptake by the serotonin transporter (SERT) and causes psychostimulant effects accompanied by hyperthermia. Since rapid increases in CNS lactate levels are suggested in response to MDMA, we investigated the effects of the physiologically-relevant increase in H(+) concentration on the two conducting states of SERT expressed in Xenopus oocytes. Perfusion with SERT substrates at pH 7.4 dose-dependently evoked a transport-associated inward current response with the following rank order of potency: 5-HT>MDMA>dopamine>>norepinephrine. In the absence of transport substrates, a step hyperpolarization pulse activated a transient Na(+) leak current, which was inhibited by SERT substrates with the same rank, as well as by a SERT inhibitor, citalopram. At pH 6.4, the K(m) values of 5-HT and dopamine for the transport-associated current were not altered, while that of MDMA was three-fold lower. In contrast, the K(i) values of all these substrates for transient leak current were unchanged at pH 6.4, suggesting that the affinities to SERT binding sites are not influenced. These results suggest that the effect of MDMA on SERT is enhanced by acidic conditions.

Authors+Show Affiliations

Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17949903

Citation

Yamauchi, Yosuke, et al. "Acceleration of Serotonin Transporter Transport-associated Current By 3,4-methylenedioxymethamphetamine (MDMA) Under Acidic Conditions." Neuroscience Letters, vol. 428, no. 2-3, 2007, pp. 72-6.
Yamauchi Y, Izumi T, Unemura K, et al. Acceleration of serotonin transporter transport-associated current by 3,4-methylenedioxymethamphetamine (MDMA) under acidic conditions. Neurosci Lett. 2007;428(2-3):72-6.
Yamauchi, Y., Izumi, T., Unemura, K., Uenishi, Y., Nakagawa, T., & Kaneko, S. (2007). Acceleration of serotonin transporter transport-associated current by 3,4-methylenedioxymethamphetamine (MDMA) under acidic conditions. Neuroscience Letters, 428(2-3), 72-6.
Yamauchi Y, et al. Acceleration of Serotonin Transporter Transport-associated Current By 3,4-methylenedioxymethamphetamine (MDMA) Under Acidic Conditions. Neurosci Lett. 2007 Nov 27;428(2-3):72-6. PubMed PMID: 17949903.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acceleration of serotonin transporter transport-associated current by 3,4-methylenedioxymethamphetamine (MDMA) under acidic conditions. AU - Yamauchi,Yosuke, AU - Izumi,Takaya, AU - Unemura,Kazuhiro, AU - Uenishi,Yoshie, AU - Nakagawa,Takayuki, AU - Kaneko,Shuji, Y1 - 2007/09/26/ PY - 2007/07/04/received PY - 2007/09/14/revised PY - 2007/09/19/accepted PY - 2007/10/24/pubmed PY - 2008/3/28/medline PY - 2007/10/24/entrez SP - 72 EP - 6 JF - Neuroscience letters JO - Neurosci. Lett. VL - 428 IS - 2-3 N2 - 3,4-Methylenedioxymethamphetamine (MDMA) selectively releases serotonin (5-HT) from neurons after uptake by the serotonin transporter (SERT) and causes psychostimulant effects accompanied by hyperthermia. Since rapid increases in CNS lactate levels are suggested in response to MDMA, we investigated the effects of the physiologically-relevant increase in H(+) concentration on the two conducting states of SERT expressed in Xenopus oocytes. Perfusion with SERT substrates at pH 7.4 dose-dependently evoked a transport-associated inward current response with the following rank order of potency: 5-HT>MDMA>dopamine>>norepinephrine. In the absence of transport substrates, a step hyperpolarization pulse activated a transient Na(+) leak current, which was inhibited by SERT substrates with the same rank, as well as by a SERT inhibitor, citalopram. At pH 6.4, the K(m) values of 5-HT and dopamine for the transport-associated current were not altered, while that of MDMA was three-fold lower. In contrast, the K(i) values of all these substrates for transient leak current were unchanged at pH 6.4, suggesting that the affinities to SERT binding sites are not influenced. These results suggest that the effect of MDMA on SERT is enhanced by acidic conditions. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/17949903/Acceleration_of_serotonin_transporter_transport_associated_current_by_34_methylenedioxymethamphetamine__MDMA__under_acidic_conditions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(07)01026-9 DB - PRIME DP - Unbound Medicine ER -