Novel PPAR gamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/259139
- author
- Heppner, TJ ; Bonev, AD ; Eckman, DM ; Gomez, Maria LU ; Petkov, GV and Nelson, MT
- organization
- publishing date
- 2005
- 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
- pmid:15452359
- 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
- 2016-04-01 16:00:33
- date last changed
- 2022-01-28 08:38:55
@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}}, keywords = {{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}}, doi = {{10.1159/000081070}}, volume = {{73}}, year = {{2005}}, }