GPR55 regulates the responsiveness to, but does not dimerise with, α1A-adrenoceptors

نویسندگان

چکیده

Emerging evidence suggests that G protein coupled receptor 55 (GPR55) may influence adrenoceptor function/activity in the cardiovascular system. Whether this reflects direct interaction (dimerization) between receptors or signalling crosstalk has not been investigated. This study explored GPR55 and alpha 1A-adrenoceptor (α1A-AR) system potential to function/signalling activities. α1A-AR mediated changes both cardiac vascular function was assessed male wild-type (WT) homozygous knockout (GPR55-/-) mice by pressure volume loop analysis isolated vessel myography, respectively. Dimerization of with examined transfected Chinese hamster ovary-K1 (CHO-K1) cells via Bioluminescence Resonance Energy Transfer (BRET). (extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation) investigated neonatal rat ventricular cardiomyocytes using AlphaScreen proximity assays. GPR55-/- exhibited enhanced pressor inotropic responses A61603 (α1A-AR agonist), while vessels, induced vasoconstriction attenuated a GPR55-dependent mechanism. Conversely, GPR55-mediated vasorelaxation altered pharmacological blockade α1A-ARs tamsulosin. While cellular studies demonstrated failed dimerize, reduced ERK1/2 phosphorylation. Taken together, provides do dimerize form heteromers, but interact at level modulate

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ژورنال

عنوان ژورنال: Biochemical Pharmacology

سال: 2021

ISSN: ['1873-2968', '0006-2952']

DOI: https://doi.org/10.1016/j.bcp.2021.114560