Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter

Tomas de Paulis, Dennis E. Schmidt, Aleksandra K. Bruchey, Michael T. Kirby, Michael Mcdonald, Patricia Commers, David M. Lovinger, Peter R. Martin

Research output: Contribution to journalArticle

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Abstract

Preliminary screening of a minor, non-xanthine constituent of roasted coffee, 3,4-diferuloyl-1,5-quinolactone (DIFEQ), showed inhibition of the adenosine transporter at low micromolar concentration. DIFEQ is a neutral derivative of the chlorogenic acids, i.e. isomeric mono- and di-substituted coumaroyl-, caffeoyl-, and feruloyl-esters of quinic acid, formed in the roasting process of coffee. Displacement of the adenosine transporter antagonist [3H](S)-(nitrobenzyl)-6-thioinosine binding by DIFEQ in cultured U-937 cell preparations, expressing the human adenosine transporter protein (hENT1), showed a Ki of 0.96±0.13 μM. Extracts of regular and decaffeinated coffee showed binding activities equivalent to 30-40 mg DIFEQ per three cups of coffee. Acute administration of a high dose of DIFEQ (100 mg/kg i.p.) reduced open field locomotion in mice for 20 min in correlation with brain levels of DIFEQ. Both 3,4-dicaffeoyl-1,5-quinide and 3,4-dicoumaroyl-1,5-quinide, two close structural analogs of DIFEQ also present in roasted coffee, showed similar affinities for the adenosine transporter, while the corresponding 3- and 4-mono caffeoyl- and feruloyl-quinides were one to two orders of magnitudes less active. This suggests that 3,4-dicinnamoyl-1,5-quinides in coffee could have the potential to raise extra-cellular adenosine levels, thereby counteracting the stimulant effect of caffeine.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalEuropean Journal of Pharmacology
Volume442
Issue number3
DOIs
StatePublished - May 10 2002

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Coffee
Chlorogenic Acid
Locomotion
Caffeine
Adenosine
adenosine transporter
Esters
Brain
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

de Paulis, T., Schmidt, D. E., Bruchey, A. K., Kirby, M. T., Mcdonald, M., Commers, P., ... Martin, P. R. (2002). Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter. European Journal of Pharmacology, 442(3), 215-223. https://doi.org/10.1016/S0014-2999(02)01540-6

Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter. / de Paulis, Tomas; Schmidt, Dennis E.; Bruchey, Aleksandra K.; Kirby, Michael T.; Mcdonald, Michael; Commers, Patricia; Lovinger, David M.; Martin, Peter R.

In: European Journal of Pharmacology, Vol. 442, No. 3, 10.05.2002, p. 215-223.

Research output: Contribution to journalArticle

de Paulis, T, Schmidt, DE, Bruchey, AK, Kirby, MT, Mcdonald, M, Commers, P, Lovinger, DM & Martin, PR 2002, 'Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter', European Journal of Pharmacology, vol. 442, no. 3, pp. 215-223. https://doi.org/10.1016/S0014-2999(02)01540-6
de Paulis, Tomas ; Schmidt, Dennis E. ; Bruchey, Aleksandra K. ; Kirby, Michael T. ; Mcdonald, Michael ; Commers, Patricia ; Lovinger, David M. ; Martin, Peter R. / Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter. In: European Journal of Pharmacology. 2002 ; Vol. 442, No. 3. pp. 215-223.
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