Abstract
AIM
To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs).
METHODS
Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips.
RESULTS
Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 μmol/L, and even ATPγS (1000 μmol/L) was infused into the cells.
CONCLUSION
Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.
TY - JOUR
T1 - The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels.
AU - Wang,Su-yang,
AU - Cui,Wen-yu,
AU - Wang,Hai,
Y1 - 2015/11/23/
PY - 2015/03/20/received
PY - 2015/07/12/accepted
PY - 2015/11/24/entrez
PY - 2015/11/26/pubmed
PY - 2016/8/19/medline
SP - 1444
EP - 50
JF - Acta pharmacologica Sinica
JO - Acta Pharmacol Sin
VL - 36
IS - 12
N2 - AIM: To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs). METHODS: Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips. RESULTS: Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 μmol/L, and even ATPγS (1000 μmol/L) was infused into the cells. CONCLUSION: Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.
SN - 1745-7254
UR - https://www.unboundmedicine.com/medline/citation/26592519/The_new_antihypertensive_drug_iptakalim_activates_ATP_sensitive_potassium_channels_in_the_endothelium_of_resistance_blood_vessels_
DB - PRIME
DP - Unbound Medicine
ER -
