Related resources
Search for item elsewhere
University researcher(s)
Academic department(s)
Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries.
Heppner T, Bonev A, Eckman D, Gomez M, Petkov G, Nelson MT
Pharmacology. 2005;73( 1):15-22.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Use our list of Related resources to find this item elsewhere. Alternatively, request a copy from the Library's Document supply service.
Abstract
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. 2005 S. Karger AG, Basel.
Keyword(s)
Algorithms; Animals; Electrophysiology; Female; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; agonists: PPAR gamma; analogs & derivatives: Tyrosine; antagonists & inhibitors: Barium; cytology: Mesenteric Arteries; cytology: Muscle, Smooth, Vascular; drug effects: Blood Pressure; drug effects: Calcium Channels; drug effects: Membrane Potentials; drug effects: Muscle Cells; drug effects: Muscle Tonus; drug effects: Vasodilation; pharmacology: Benzophenones; pharmacology: Hypoglycemic Agents; pharmacology: Oxazoles; pharmacology: Thiazolidinediones