The hypolipidemic drug metabolites nafenopin-CoA and ciprofibroyl-CoA are competitive P2Y<sub>1</sub> receptor antagonists

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dc.contributor.authorCoddou, C
dc.contributor.authorLoyola, G
dc.contributor.authorBoyer, JL
dc.contributor.authorBronfman, M
dc.contributor.authorHuidobro-Toro, JP
dc.date.accessioned2025-01-21T01:09:43Z
dc.date.available2025-01-21T01:09:43Z
dc.date.issued2003
dc.description.abstractCoenzyme A (CoA-SH), endogenous and drug-derived CoA-derivatives were tested as putative antagonists of P2Y receptors expressed in Xenopus laevis oocytes, a method used to determine calcium-activated chloride current, an indicator of the activation of these receptors. CoA-SH antagonized reversibly and in a concentration-dependent manner the ATP-gated currents evoked by the human P2Y(1) but not the P2Y(2) receptor. Palmitoyl-CoA was four-fold more potent than CoASH as an antagonist while palmitoyl-carnitine was inactive, highlighting the role of the CoA-SH moiety in the antagonism. The CoA derivatives of nafenopin and ciprofibrate, two clinically relevant hypolipidemic drugs, increased 13 and three-fold the potency of CoA-SH, respectively. The K(B)s of nafenopin-CoA and ciprofibroyl-CoA were 58 and 148 nM, respectively; the slopes of the Schild plots were unitary. Neither 100 muM nafenopin nor ciprofibrate alone altered the P2Y, receptor activity. Neither CoA-SH nor ciprofibroyl-CoA antagonized the rat P2X(2) or the P2X(4) nucleotide receptors nor interacted with the 5-HT2A/C receptors. The bulky drug CoA-SH derivatives identify a hydrophobic pocket, which may serve as a potential target for novel selective P2Y(1) antagonists. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
dc.fuente.origenWOS
dc.identifier.doi10.1016/S0014-5793(03)00044-9
dc.identifier.issn0014-5793
dc.identifier.urihttps://doi.org/10.1016/S0014-5793(03)00044-9
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96612
dc.identifier.wosidWOS:000181009100028
dc.issue.numero1-3
dc.language.isoen
dc.pagina.final150
dc.pagina.inicio145
dc.revistaFebs letters
dc.rightsacceso restringido
dc.subjectP2Y1 receptor antagonists
dc.subjectacyl-CoA derivatives
dc.subjectpalmitoyl-CoA
dc.subjectfibrates
dc.subjecthypolipidemic drugs
dc.subjectnafenopin-CoA
dc.subjectciprofibroyl-CoA
dc.subjectcompetitive antagonism
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe hypolipidemic drug metabolites nafenopin-CoA and ciprofibroyl-CoA are competitive P2Y<sub>1</sub> receptor antagonists
dc.typeartículo
dc.volumen536
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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