2016
DOI: 10.1126/scisignal.aac9187
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Abstract: The angiotensin (Ang) type 1 receptor (AT1R) promotes functional and structural integrity of the arterial wall to contribute to vascular homeostasis, but this receptor also promotes hypertension. In our investigation of how Ang II signals are converted by the AT1R from physiological to pathological outputs, we found that the purinergic P2Y6 receptor (P2Y6R), an inflammation-inducible G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR), promoted Ang II-induced hypertension in m… Show more

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Cited by 65 publications
(51 citation statements)
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“…When subjected to AngII treatment (1 mg/kg per day for 3 weeks), P2ry6 −/− mice displayed reduced hypertension compared with wild-type littermates (Figure VI in the online-only Data Supplement). Resistance to AngII-dependent hypertension was recently reported, 15 consistent with a P2Y 6 receptor effect on blood pressure regulation in pathological conditions.…”
Section: Resultssupporting
confidence: 71%
“…When subjected to AngII treatment (1 mg/kg per day for 3 weeks), P2ry6 −/− mice displayed reduced hypertension compared with wild-type littermates (Figure VI in the online-only Data Supplement). Resistance to AngII-dependent hypertension was recently reported, 15 consistent with a P2Y 6 receptor effect on blood pressure regulation in pathological conditions.…”
Section: Resultssupporting
confidence: 71%
“…However, we cannot define which effect preferably increased NO or suppressed prostanoid productions upon MRS2578-sensitive P2Y 6 receptor stimulation by UDP. Furthermore, the possible mechanisms underlying the activation of other receptors, such as GPR17 [36], or heterodimers, such as angiotensin type 1/P2Y 6 receptors [37,38], in our findings may be related to UDP-mediated responses. Because contrasting trends are observed in UDP-induced contraction in endothelium-denuded aorta between the groups, that is, between the basal and PE-precontracted aorta, the role of P2Y 6 (probably MRS2578-sensitive receptor) in contraction may also be different between OLETF and LETO rat aortas.…”
Section: Resultsmentioning
confidence: 88%
“…One possible explanation for this may be that P2Y 6 receptors exist as a heterodimer, which has led to an altered agonist profile in these cells. P2Y 6 receptors have been shown to form heterodimers with other GPCRs [37,38] and heterooligomerization of other P2Y receptors can alter the agonist sensitivity of these receptors [39]. After the initial peak, blockade of the ADP response with MRS2578 leads to a decrease in the concentration of intracellular Ca 2+ to below baseline Ca 2+ levels, suggesting there is either efflux or internalisation of Ca…”
Section: Discussionmentioning
confidence: 99%