Linked Life Data

1645340

Source:http://linkedlifedata.com/resource/pubmed/id/1645340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1991-7-1
pubmed:abstractText
L-651,582, 5-amino-[4-(4-chlorobenzoyl)-3,5-dichlorobenzyl]-1,2,3-triazole-4- carboxamide, an antiproliferative and antiparasitic agent previously shown to affect 45Ca2+ uptake into mammalian cells, inhibits both receptor-mediated and voltage-dependent calcium entry in well characterized in vitro systems. Indo 1 fluorescence measurements of cytosolic calcium levels indicate that the drug has no effect on the initial transient release of internal stores of calcium stimulated by fMet-Leu-Phe in rat polymorphonuclear leukocytes. It does decrease the levels maintained subsequently, however, indicating blockage of calcium influx through receptor-operated channels. L-651,582 also blocks the stimulation of leukotriene B4 (LTB4) production by fMet-Leu-Phe with an IC50 = 0.5 micrograms/ml equal to that for calcium entry inhibition. The LTB4 inhibition is likely due to calcium entry inhibition since L-651,582 does not inhibit calmodulin or enzymes producing arachidonate metabolites. L-651,582 also inhibits potassium-stimulated 45Ca2+ influx into GH3 cells with an IC50 of 0.5 microgram/ml, indicating a block of voltage-gated L-type calcium channels. Patch voltage clamp measurements of current through L- and T-type calcium in guinea pig atrial cells also indicate that L-651,582 is a calcium antagonist. Block of L-type calcium channels is voltage-dependent, and the apparent dissociation constant for the high affinity state is 0.2 micrograms/ml. The IC50 for block of T-type calcium channels is 1.4 micrograms/ml. The inhibition of cellular proliferation and the production of arachidonate metabolites by L-651,582 may be the result of the nearly equipotent block of receptor-operated and voltage-gated calcium channels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10136-42
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
The inhibition of receptor-mediated and voltage-dependent calcium entry by the antiproliferative L-651,582.
pubmed:affiliation
Department of Enzymology, Merck Institute for Therapeutic Research, Rahway, New Jersey 07065.
pubmed:publicationType
Journal Article