Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo.

Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Research Abstract Details 

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Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Abstract Text:

Qi Wang,Marilyn E Morris,

The objective of this study was to determine the effects of flavonoids on the in vitro monocarboxylate transporter 1 (MCT1)-mediated transport and in vivo disposition of the drug of abuse, gamma-hydroxybutyrate (GHB). The uptake of GHB in rat MCT1 gene-transfected MDA-MB231 cells was significantly decreased in the presence of the flavonoids apigenin, biochanin A, chrysin, diosemin, fisetin, genistein, hesperitin, kaempferol, luteolin, morin, narigenin, phloretin, and quercetin, but was not affected by the flavonoid glycosides phloridzin and rutin. The IC(50) values for luteolin, morin, and phloretin were 0.41 +/- 0.14, 6.41 +/- 2.01, and 2.57 +/- 0.48 microM, with the inhibition mechanism for luteolin being competitive. [(3)H]Kaempferol and [(3)H]biochanin A did not exhibit MCT1-mediated uptake, suggesting that these flavonoids are not substrates for MCT1. The combination of luteolin and phloretin inhibited the uptake of GHB in a synergistic manner; however, the combination of luteolin and morin was antagonistic. GHB 1000 mg/kg was administered to rats by i.v. bolus, with or without the concomitant administration of luteolin 10 mg/kg i.v. After luteolin treatment, the renal and total clearances of GHB were significantly increased, probably because of inhibition of the MCT1-mediated renal reabsorption of GHB, and the sleep time significantly decreased (121 +/- 5 min versus 165 +/- 10 min) compared with control rats. Overall, the results of this study indicate that flavonoids from food or herbal products may significantly alter the pharmacokinetics and pharmacodynamics of MCT substrates.

Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Publishing Authors By Initials

Q Wang,ME Morris,

For similar proteins: carrier proteins: membrane transport proteins: ion pumps: symporters research abstracts see: proteins: carrier proteins: membrane transport proteins: ion pumps: symporters research

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Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Drug metabolism and disposition: the biological fa

VOLUME: 35

Page Numbers: 201-8

Journal Abbreviation: Drug Metab. Dispos.

ISSN: 0090-9556

DAY: 15

MONTH: 11

YEAR: 2006

Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9421550

Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Keywords Mesh Terms:

KEYWORDS: Symporters

MESH TERMS: physiology

Chemical & Substance for Abstract: Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Information

Substance Name: Sodium Oxybate

Registry Number: 502-85-2

Grant and Affiliation Information for Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo.

AFFILIATION: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.

Country: United States

AGENCY: United States NIDA

GRANT: DA14988

ACRONYM: DA

MEDLINETA: Drug Metab Dispos

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