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1.
Langmuir ; 29(50): 15655-63, 2013 Dec 17.
Article in English | MEDLINE | ID: mdl-24289276

ABSTRACT

One aspect of the attempt to restrain global warming is the reduction of the levels of atmospheric CO2 produced by fossil fuel power systems. This study attempted to develop a method that reduces CO2 emissions by investigating the absorption of CO2 into sterically hindered amine 2-amino-2-methyl-1-propanol (AMP), the acceleration of the absorption rate by using the enzyme carbonic anhydrase (CA), and the conversion of the absorption product to stable carbonates. CO2 absorbed by AMP is converted via a zwitterion mechanism to bicarbonate species; the presence of these anions was confirmed with (1)H and (13)C NMR spectral analysis. The catalytic efficiency (kcat/Km), CO2 absorption capacities, and enthalpy changes (ΔHabs) of aqueous AMP in the presence or absence of CA were found to be 2.61 × 10(6) or 1.35 × 10(2) M(-1) s(-1), 0.97 or 0.96 mol/mol, and -69 or -67 kJ/mol, respectively. The carbonation of AMP-absorbed CO2 was performed by using various Ca(2+) sources, viz., CaCl2 (CAC), Ca(OOCCH3)2 (CAA), and Ca(OOCCH2CH3)2 (CAP), to obtain various polymorphs of CaCO3. The yields of CaCO3 from the Ca(2+) sources were found in the order CAP > CAA > CAC as a result of the effects of the corresponding anions. CAC produces pure rhombohedral calcite, and CAA and CAP produce the unusual phase transformation of calcite to spherical vaterite crystals. Thus, AMP in combination with CAA and CAP can be used as a CO2 absorbent and buffering agent for the sequestration of CO2 in porous CaCO3.

2.
J Pharmacol Sci ; 123(1): 67-77, 2013 Sep 20.
Article in English | MEDLINE | ID: mdl-24005046

ABSTRACT

Azelastine is a second generation histamine H1-receptor antagonist used as an anti-asthmatic and anti-allergic drug that can induce QT prolongation and torsades de pointes. We investigated the acute effects of azelastine on human ether-a-go-go-related gene (hERG) channels, action potential duration (APD), and L-type (I(Ca,L)) and T-type Ca²âº current (I(Ca,T)) to determine the electrophysiological basis for its proarrhythmic potential. Azelastine increased the APD at 90% of repolarization concentration dependently, with an IC50 of 1.08 nM in guinea-pig ventricular myocytes. We examined the effects of azelastine on the hERG channels expressed in Xenopus oocytes and HEK293 cells using two-microelectrode voltage-clamp and patch-clamp techniques. Azelastine induced a concentration-dependent decrease of the hERG current amplitude at the end of the voltage steps and tail currents. The IC50 for the azelastine-induced block of the hERG currents expressed in HEK293 cells was 11.43 nM, while the drug inhibited I(Ca,L) and I(Ca,T) with IC50 values of 7.60 and 26.21 µM, respectively. The S6 domain mutations, Y652A partially attenuated and F656A abolished hERG current block. These results suggest that azelastine is a potent blocker of hERG channels rather than I(Ca,L) or I(Ca,T), providing molecular mechanisms for the arrhythmogenic side effects during the clinical administration of azelastine.


Subject(s)
Action Potentials/drug effects , Arrhythmias, Cardiac/chemically induced , Calcium Channels, L-Type/metabolism , Calcium Channels, T-Type/metabolism , Electrophysiological Phenomena/drug effects , Ether-A-Go-Go Potassium Channels/antagonists & inhibitors , Histamine H1 Antagonists/adverse effects , Histamine H1 Antagonists/pharmacology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/physiology , Phthalazines/adverse effects , Phthalazines/pharmacology , Animals , Cells, Cultured , Dose-Response Relationship, Drug , ERG1 Potassium Channel , Ether-A-Go-Go Potassium Channels/chemistry , Ether-A-Go-Go Potassium Channels/metabolism , Guinea Pigs , HEK293 Cells , Heart Ventricles/cytology , Humans , Oocytes , Patch-Clamp Techniques , Protein Structure, Tertiary , Xenopus laevis
3.
Eur J Pharmacol ; 637(1-3): 138-47, 2010 Jul 10.
Article in English | MEDLINE | ID: mdl-20399767

ABSTRACT

The slowly activating delayed rectifier K(+) channels (I(Ks)) are one of the main pharmacological targets for development of drugs against cardiovascular diseases. Cardiac I(Ks) consists of KCNQ1 plus KCNE1 subunits. Ginsenoside, one of the active ingredient of Panax ginseng, enhances cardiac I(Ks) currents. However, little is known about the molecular mechanisms of how ginsenoside interacts with channel proteins to enhance cardiac I(Ks). In the present study, we investigated ginsenoside Rg(3) (Rg(3)) effects on human I(Ks) by co-expressing human KCNQ1 plus KCNE1 subunits in Xenopus oocytes. Rg(3) enhanced I(Ks) currents in concentration- and voltage-dependent manners. The EC(50) was 15.2+/-8.7 microM. However, in oocytes expressing KCNQ1 alone, Rg(3) inhibited the currents with concentration- and voltage-dependent manners. The IC(50) was 4.8+/-0.6 microM. Since Rg(3) acts opposite ways in oocytes expressing KCNQ1 alone or KCNQ1 plus KCNE1 subunits, we examined Rg(3) effects after co-expression of different ratios of KCNE1 and KCNQ1. The increase of KCNE1/KCNQ1 ratio converted I(Ks) inhibition to I(Ks) activations. One to ten ratio of KCNE1 and KCNQ1 subunit is required for Rg(3) activation of I(Ks). Mutations of K318 and V319 into K318Y and V319Y of KCNQ1 channel abolished Rg(3) effects on KCNQ1 or KCNQ1 plus KCNE1 channel currents. The docked modeling revealed that K318 residue plays a key role in stabilization between Rg(3) and KCNQ1 plus KCNE1 or KCNQ1 subunit. These results indicate that Rg(3)-induced activation of I(Ks) requires co-assembly of KCNQ1 and KCNE1 subunits and achieves this through interaction with residues K318 and V319 of KCNQ1 subunit.


Subject(s)
Ginsenosides/pharmacology , Ion Channel Gating/drug effects , KCNQ1 Potassium Channel/agonists , KCNQ1 Potassium Channel/metabolism , Potassium Channels, Voltage-Gated/chemistry , Potassium Channels, Voltage-Gated/metabolism , Protein Subunits/metabolism , Action Potentials/drug effects , Animals , Base Sequence , Catalytic Domain , Dose-Response Relationship, Drug , Humans , Ion Channel Gating/genetics , Ion Channel Gating/physiology , KCNQ1 Potassium Channel/chemistry , KCNQ1 Potassium Channel/genetics , Lysine/metabolism , Mutation , Oocytes/metabolism , Panax/chemistry , Potassium Channels, Voltage-Gated/genetics , Protein Subunits/chemistry , Protein Subunits/genetics , Valine/metabolism , Xenopus laevis
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