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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries.

Novel non-thiazolidinedione, tyrosine-derived peroxisome proliferator-activated receptor gamma agonists, GI 262570, GW 7845, GW 1929, developed by GlaxoSmithKline (GSK) along with pioglitazone and nisoldipine, were studied on currents through L-type voltage-dependent calcium channels (VDCC) in freshly isolated smooth muscle cells from mesenteric arteries, and on the diameter of pressurized mesenteric arteries in vitro. Using Ba2+ (10 mmol/l) as the charge carrier through VDCC, the half-inhibition constants (IC50) for GI 262570, GW 7845, GW 1929, and pioglitazone were 2.0 +/- 0.5, 3.0 +/- 0.5, 5.0 +/- 0.7, and 10.0 +/- 0.8 mumol/l, respectively. For arterial diameter measurements the IC50 values for GI 262570, GW 7845, GW 1929, and pioglitazone were 2.4, 4.1, 6.3, and 13.9 mumol/l, respectively. Each GSK compound and pioglitazone was effective at inhibiting VDCC and relaxing pressurized arteries, suggesting that the vasodilation of resistance arteries could be explained by the inhibition of calcium entry through VDCC.[1]

References

  1. Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries. Heppner, T.J., Bonev, A.D., Eckman, D.M., Gomez, M.F., Petkov, G.V., Nelson, M.T. Pharmacology (2005) [Pubmed]
 
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