Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5775
Title: Cardamonin is a bifunctional vasodilator that inhibits Cav1.2 current and stimulates KCa1.1 current in rat tail artery myocytes
Authors: Fusi, Fabio 
Cavalli, M
Mulholland, D
CROUCH N., R
Coombes, P
Dawson, G
Bova, S
Sgaragli, G.
Saponara, Simona
Issue Date: 2010
Project: None 
Journal: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Abstract: 
An in-depth analysis of the effects of cardamonin, 2',4'-dihydroxy-6'-methoxychalcone, on rat tail artery preparations was performed by means of whole-cell patch-clamp recordings of Ca(v)1.2 Ca(2+) [I(Ca(L))] or Ba(2+) [I(Ba(L))] current as well as K(Ca)1.1 currents in single myocytes and by measuring contractile responses in endothelium-denuded isolated rings. At a holding potential (V(h)) of -80 mV, cardamonin decreased both I(Ba(L)) and I(Ca(L)) in a concentration-dependent manner with similar pIC(50) values. The maximum of the I(Ba(L))-voltage relationship was shifted by 10 mV in the hyperpolarizing direction, but threshold remained unaffected. Cardamonin modified both the activation and the inactivation kinetics of I(Ba(L)) and shifted the voltage dependence of both inactivation and activation curves to more negative potentials by 19 and 7 mV, respectively, thus markedly decreasing the Ba(2+) window current. Block of I(Ba(L)) was frequency-dependent, and rate of recovery from inactivation was slowed. Cardamonin increased K(Ca)1.1 currents in a concentration-dependent manner; this stimulation was iberiotoxin- and BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid]-sensitive. On the contrary, iberiotoxin did not modify cardamonin-induced relaxation of rings precontracted either with phenylephrine or with (S)-(-)-methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate [(S)-(-)-Bay K 8644]. The overall effects of cardamonin were incompletely reversed by washout. In conclusion, cardamonin is a naturally occurring, bifunctional vasodilator that, by simultaneously inhibiting I(Ca(L)) and stimulating K(Ca)1.1 current, may represent a scaffold for the design of novel drugs of potential interest for treatment of systemic hypertension.
Description: 
34991
URI: http://hdl.handle.net/20.500.12779/5775
ISSN: 0022-3565
DOI: 10.1124/jpet.109.161265
Appears in Collections:Publications

Show full item record

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.