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- W2020902968 abstract "The A 1 adenosine receptor (A 1 AR) is coupled to G i /G o proteins, but the downstream signaling pathways in smooth muscle cells are unclear. This study was performed in coronary artery smooth muscle cells (CASMCs) isolated from the mouse heart [A 1 AR wild type (A 1 WT) and A 1 AR knockout (A 1 KO)] to delineate A 1 AR signaling through the PKC pathway. In A 1 WT cells, treatment with (2 S)- N 6 -(2-endo-norbornyl)adenosine (ENBA; 10 −5 M) increased A 1 AR expression by 150%, which was inhibited significantly by the A 1 AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (10 −6 M), but not in A 1 KO CASMCs. PKC isoforms were identified by Western blot analysis in the cytosolic and membrane fractions of cell homogenates of CASMCs. In A 1 WT and A 1 KO cells, significant levels of basal PKC-α were detected in the cytosolic fraction. Treatment with the A 1 AR agonist ENBA (10 −5 M) translocated PKC-α from the cytosolic to membrane fraction significantly in A 1 WT but not A 1 KO cells. Phospholipase C isoforms (βI, βIII, and γ 1 ) were analyzed using specific antibodies where ENBA treatment led to the increased expression of PLC-βIII in A 1 WT CASMCs while having no effect in A 1 KO CASMCs. In A 1 WT cells, ENBA increased PKC-α expression and p42/p44 MAPK (ERK1/2) phospohorylation by 135% and 145%, respectively. These effects of ENBA were blocked by Gö-6976 (PKC-α inhibitor) and PD-98059 (p42/p44 MAPK inhibitor). We conclude that A 1 AR stimulation by ENBA activates the PKC-α signaling pathway, leading to p42/p44 MAPK phosphorylation in CASMCs." @default.
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- W2020902968 date "2009-09-01" @default.
- W2020902968 modified "2023-10-06" @default.
- W2020902968 title "A<sub>1</sub> adenosine receptor-mediated PKC and p42/p44 MAPK signaling in mouse coronary artery smooth muscle cells" @default.
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- W2020902968 doi "https://doi.org/10.1152/ajpheart.00374.2009" @default.
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