Linked Life Data

12011649

Source:http://linkedlifedata.com/resource/pubmed/id/12011649

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-5-15
pubmed:abstractText
Cilnidipine is a novel dihydropyridine (DHP) antagonist. However, its pharmacological effects on vascular DHP-sensitive L-type channels and protein kinase C (PKC)-mediated arterial contraction is incompletely understood. To address this issue, we studied the effects of cilnidipine on multi-subunit, C-class L-type Ca2+ channels in rat aortic A7r5 cells, as well as on Ca2+ channel (L-type) alpha1C-b and (T-type) alpha1G subunits in the Xenopus oocyte expression system. Cilnidipine dose- and time-dependently inhibited Ba2+ currents in A7r5 cells, with half-maximal inhibitions (IC50) at 10 nmol/l after 10 min. Unlike classical pharmacological Ca2+ channel blockers, cilnidipine's block of Ca2+ currents did not reach steady-state levels within 10 min, indicating steady-state half-maximal inhibition of native, multi-subunit L-type channels at < 10 nmol/l. In contrast, smooth muscle alpha1Cb currents were blocked by cilnidipine at much higher doses (steady-state IC50, 20 micromol/l) whereas alpha1G currents were not inhibited by cilnidipine (30 micromol/l). Cilnidipine dose-dependently inhibited depolarization- and Ca2+-induced contractions of rat aortic rings, with an IC50 of 10 nmol/l at 10 min. However, the onset of the effects was very slow, with approximately 71% inhibition by 3 nmol/l cilnidipine after 90 min exposure to cilnidipine. In contrast, cilnidipine did not inhibit phorbol 12-myristate-13-acetate (100 nmol/l)-mediated contractions. We conclude that cilnidipine represents an extremely slow-acting DHP that targets multi-subunit L-type channels, but not PKC in arterial smooth muscle. Because cilnidipine is less potent in cells expressing the pore-forming alpha1C-b subunit, the data further suggest that this unique slow-acting mechanism of cilnidipine is mediated by a complex interaction of cilnidipine with alpha1C-b and accessory channel subunits.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0263-6352
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
885-93
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Cilnidipine is a novel slow-acting blocker of vascular L-type calcium channels that does not target protein kinase C.
pubmed:affiliation
Franz Volhard Clinic, Humboldt University of Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't