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

Heppner, TJ; Bonev, AD; Eckman, DM; Gomez, Maria LU ; Petkov, GV and Nelson, MT (2005) In Pharmacology 73(1). p.15-22
Abstract
Novel non-thiazolidinedione, tyrosine-derived peroxisome proliferator-activated receptor gamma agonists, GI 262570, GW 7845, GW 1929, developed by Glaxo-Smith-Kline (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... (More)
Novel non-thiazolidinedione, tyrosine-derived peroxisome proliferator-activated receptor gamma agonists, GI 262570, GW 7845, GW 1929, developed by Glaxo-Smith-Kline (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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
voltage-dependent calcium channels, calcium-activated K+ channels, peroxisome proliferator-activated receptors
in
Pharmacology
volume
73
issue
1
pages
15 - 22
publisher
Karger
external identifiers
  • pmid:15452359
  • wos:000225766000003
  • scopus:10844281766
ISSN
1423-0313
DOI
10.1159/000081070
language
English
LU publication?
yes
id
0fd6284b-dca4-4ade-8092-4631cf00ba2d (old id 259139)
date added to LUP
2007-08-20 11:50:41
date last changed
2017-01-01 06:53:10
@article{0fd6284b-dca4-4ade-8092-4631cf00ba2d,
  abstract     = {Novel non-thiazolidinedione, tyrosine-derived peroxisome proliferator-activated receptor gamma agonists, GI 262570, GW 7845, GW 1929, developed by Glaxo-Smith-Kline (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.},
  author       = {Heppner, TJ and Bonev, AD and Eckman, DM and Gomez, Maria and Petkov, GV and Nelson, MT},
  issn         = {1423-0313},
  keyword      = {voltage-dependent calcium channels,calcium-activated K+ channels,peroxisome proliferator-activated receptors},
  language     = {eng},
  number       = {1},
  pages        = {15--22},
  publisher    = {Karger},
  series       = {Pharmacology},
  title        = {Novel PPAR gamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries},
  url          = {http://dx.doi.org/10.1159/000081070},
  volume       = {73},
  year         = {2005},
}