@article{APS3528,
author = {Hua-mei HE and Chao-liang LONG and Le-zhi ZHANG and Ai-ling FU and Hai WANG},
title = {Alteration of binding sites for [ 3 H]P1075 and [ 3 H]glibenclamide in renovascular hypertensive rat aorta 1 },
journal = {Acta Pharmacologica Sinica},
volume = {26},
number = {1},
year = {2016},
keywords = {},
abstract = {Aim: The alterations of the binding sites for ATP-sensitive K+ channel (KATP)
openers and blockers in aortic strips were investigated in hypertensive rats.
Methods: Radioligand binding techniques were used to compare the specific binding
properties of [3H]P1075 and [3H]glibenclamide (Gli) in normotensive (NWR)
and reno-vascular hypertensive rat (RVHR) aortic strips.
Results: The KD values
of [3H]P1075 binding were increased by 1.5-fold, while the Bmax values were unchanged
in RVHR. The IC50 values of P1075 and pinacidil (Pin) for displacing
the [3H]P1075 binding in RVHR were increased by 1.8- and 1.7-fold, respectively.
The kinetic processes of association and dissociation of [3H]P1075 binding were
slower in RVHR. Glibenclamide pretreatment slowed down the kinetic processes
of the association and dissociation of [3H]P1075 binding in NWR, but failed to
alter the kinetic processes of [3H]P1075 binding in RVHR. The IC50 values of Gli
for displacing the [3H]Gli binding at high-affinity sites were increased by 3-fold,
while those at low-affinity sites remained to be unchanged in RVHR. The kinetic
processes of association of [3H]Gli binding were decreased and those of the dissociation
were accelerated in RVHR. The treatment with Pin slowed down the
association kinetic processes but accelerated the process of the dissociation of
[3H]Gli binding in NWR, but did not alter the kinetics of [3H]Gli binding in RVHR.
Conclusion: The affinity of binding sites for [3H]P1075 and of high-affinity binding
sites for [3H]Gli are decreased, and the negative allosteric interactions between
the two binding sites are impaired in RVHR aorta.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3528}
}