| First Author | Prada MP | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 30821687 | Mgi Jnum | J:275993 |
| Mgi Id | MGI:6304090 | Doi | 10.7554/eLife.42214 |
| Citation | Prada MP, et al. (2019) A Gs-coupled purinergic receptor boosts Ca(2+) influx and vascular contractility during diabetic hyperglycemia. Elife 8:e42214 |
| abstractText | Elevated glucose increases vascular reactivity by promoting L-type CaV1.2 channel (LTCC) activity by protein kinase A (PKA). Yet, how glucose activates PKA is unknown. We hypothesized that a Gs-coupled P2Y receptor is an upstream activator of PKA mediating LTCC potentiation during diabetic hyperglycemia. Experiments in apyrase-treated cells suggested involvement of a P2Y receptor underlying the glucose effects on LTTCs. Using human tissue, expression for P2Y11, the only Gs-coupled P2Y receptor, was detected in nanometer proximity to CaV1.2 and PKA. FRET-based experiments revealed that the selective P2Y11 agonist NF546 and elevated glucose stimulate cAMP production resulting in enhanced PKA-dependent LTCC activity. These changes were blocked by the selective P2Y11 inhibitor NF340. Comparable results were observed in mouse tissue, suggesting that a P2Y11-like receptor is mediating the glucose response in these cells. These findings established a key role for P2Y11 in regulating PKA-dependent LTCC function and vascular reactivity during diabetic hyperglycemia. |
