Dataset Information

Bidirectional Control of Coronary Vascular Resistance by Eicosanoids via a Novel GPCR

ABSTRACT: Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We identified G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor antagonistically regulated by two endogenous eicosanoids: 15-HETE, which stimulates GPR39 to increase mVSMC intracellular calcium and augment microvascular CVR, and 14,15-EET, which inhibits these actions. Furthermore, zinc ion acts as an allosteric modulator of GPR39 to potentiate the efficacy of the two ligands. The study elucidates the roles of eicosanoids in cardiovascular physiology and disease and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.

INSTRUMENT(S): LTQ, LTQ Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Smooth Muscle Cell

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Phillip Wilmarth

LAB HEAD: Nabil J. Alkayed

PROVIDER: PXD013952 | Pride | 2022-04-13

REPOSITORIES: Pride

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Publications

Control of coronary vascular resistance by eicosanoids via a novel GPCR.

Alkayed Nabil J NJ Cao Zhiping Z Qian Zu Yuan ZY Nagarajan Shanthi S Liu Xuehong X Nelson Jonathan W JW Xie Fuchun F Li Bingbing B Fan Wei W Liu Lijuan L Grafe Marjorie R MR Davis Catherine M CM Xiao Xiangshu X Barnes Anthony P AP Kaul Sanjiv S

American journal of physiology. Cell physiology 20220406 5

Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We applied a chemoproteomics strategy using a clickable photoaffinity probe to identify G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor selective for two endogenous eicosanoids, 15-HETE and 14,15-EET, which act o ...[more]

PMID: 35385329

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Dataset Information

Bidirectional Control of Coronary Vascular Resistance by Eicosanoids via a Novel GPCR

Publications

Control of coronary vascular resistance by eicosanoids via a novel GPCR.

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