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- Title
Multidrug resistance protein 4 mediates cAMP efflux from rat preglomerular vascular smooth muscle cells.
- Authors
Cheng, Dongmei; Ren, Jin; Jackson, Edwin K
- Abstract
1. Previous studies have shown that stimulation of adenylyl cyclase in preglomerular vascular smooth muscle cells (PGVSMC) increases extracellular cAMP; however, the mechanism by which PGVSMC transport intracellular cAMP into the extracellular milieu is unknown. 2. We hypothesize that multidrug resistance protein (MRP) 4 is the primary transporter mediating efflux of intracellular cAMP from PGVSMC. 3. Both reverse transcription–polymerase chain reaction and real-time polymerase chain reaction detected MRP4 mRNA in PGVSMC in culture. Moreover, western blotting using an antibody specific for MRP4 gave rise to a 150 kDa signal, consistent with the presence of MRP4 protein in PGVSMC. 4. Specifically designed short interference (si) RNA reduced MRP4 mRNA expression by 71% ( P = 0.0075) and MRP4 protein by 80% ( P = 0.0004). 5. Isoproterenol (1 μmol/L) increased intracellular cAMP, which resulted in efflux of cAMP into the medium. The siRNA knockdown of MRP4 significantly reduced basal extracellular cAMP and nearly abolished isoproterenol-induced increases in extracellular cAMP ( P = 0.0143, interaction between isoproterenol and MRP4 siRNA in two-factor analysis of variance). In isoproterenol-treated cells, MRP4 siRNA decreased the ratio of extracellular cAMP to intracellular cAMP by 72% ( P = 0.0019). 6. We conclude that MRP4 is the dominant cAMP transporter in PGVSMC.
- Subjects
MULTIDRUG resistance; ADENOSINE monophosphate; VASCULAR smooth muscle physiology; REVERSE transcriptase polymerase chain reaction; CELL physiology
- Publication
Clinical & Experimental Pharmacology & Physiology, 2010, Vol 37, Issue 2, p205
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/j.1440-1681.2009.05272.x