Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes.

Article Details

Citation

Furukawa T, Nukada T, Namiki Y, Miyashita Y, Hatsuno K, Ueno Y, Yamakawa T, Isshiki T

Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes.

Eur J Pharmacol. 2009 Jun 24;613(1-3):100-7. doi: 10.1016/j.ejphar.2009.04.036. Epub 2009 May 3.

PubMed ID
19401195 [ View in PubMed
]
Abstract

1,4-dihydropyridine (DHP) Ca(2+) antagonists have recently been shown to block T-type Ca(2+) channels, which may render favorable actions on cardiovascular systems. However, this evaluation remains to be done systematically for each T-type Ca(2+) channel subtype except for the Ca(v)3.1 (alpha(1G)) subtype. To address this issue at the molecular level, blocking effects of 14 kinds of DHPs (amlodipine, aranidipine, azelnidipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nitrendipine), which are clinically used for treatments of hypertension, on 3 subtypes of T-type Ca(2+) channels [Ca(v)3.2 (alpha(1H)), Ca(v)3.3 (alpha(1I)), and Ca(v)3.1 (alpha(1G))] were investigated in the Xenopus oocyte expression system using the two-microelectrode voltage-clamp technique. These 3 kinds (alpha(1H), alpha(1I) and alpha(1G)) of T-type channels were blocked by amlodipine, manidipine and nicardipine. On the other hand, azelnidipine, barnidipine, benidipine and efonidipine significantly blocked alpha(1H) and alpha(1G), but not alpha(1I) channels, while nilvadipine and nimodipine apparently blocked alpha(1H) and alpha(1I), but not alpha(1G) channels. Moreover, aranidipine blocked only alpha(1H) channels. By contrast, cilnidipine, felodipine, nifedipine and nitrendipine had little effects on these subtypes of T-type channels. The result indicates that the blockade of T-type Ca(2+) channels by derivatives of DHP Ca(2+) antagonist was selective for the channel subtype. Therefore, these selectivities of DHPs in blocking T-type Ca(2+) channel subtypes would provide useful pharmacological and clinical information on the mode of action of the drugs including side-effects and adverse effects.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AranidipineVoltage-dependent T-type calcium channel subunit alpha-1HProteinHumans
Unknown
Inhibitor
Details
BarnidipineVoltage-dependent T-type calcium channel subunit alpha-1GProteinHumans
Unknown
Antagonist
Inhibitor
Details
BarnidipineVoltage-dependent T-type calcium channel subunit alpha-1HProteinHumans
Unknown
Antagonist
Inhibitor
Details
EfonidipineVoltage-dependent T-type calcium channel subunit alpha-1GProteinHumans
Yes
Inhibitor
Details
EfonidipineVoltage-dependent T-type calcium channel subunit alpha-1HProteinHumans
Yes
Inhibitor
Details
ManidipineVoltage-dependent T-type calcium channel subunit alpha-1GProteinHumans
Unknown
Inhibitor
Details
ManidipineVoltage-dependent T-type calcium channel subunit alpha-1HProteinHumans
Unknown
Inhibitor
Details
ManidipineVoltage-dependent T-type calcium channel subunit alpha-1IProteinHumans
Unknown
Inhibitor
Details
NicardipineVoltage-dependent T-type calcium channel subunit alpha-1GProteinHumans
Unknown
Inhibitor
Details
NicardipineVoltage-dependent T-type calcium channel subunit alpha-1HProteinHumans
Unknown
Inhibitor
Details
NicardipineVoltage-dependent T-type calcium channel subunit alpha-1IProteinHumans
Unknown
Inhibitor
Details
NilvadipineVoltage-dependent T-type calcium channel subunit alpha-1HProteinHumans
Unknown
Inhibitor
Details
NilvadipineVoltage-dependent T-type calcium channel subunit alpha-1IProteinHumans
Unknown
Inhibitor
Details