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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1993-6-22
|
| pubmed:abstractText |
Antioxidants and T-type Ca channel antagonists are neuroprotective during ischemia or other central nervous system traumas. U-88779E (1-[(4-chlorophenyl-phenyl)-methyl]-4-[(7-methoxy-5-isopropyl- 2,4,6-cycloheptatrien-1-one)-2-methyl]piperazine) has been shown to have both antioxidant activity and the ability to block Ca fluxes in cardiac microsomes. In this study, we examined the effect of U-88779E on Ca, Na and K channels in a neuronal cell line, N1E-115 cells. The drug blocked transient barium current (IBa) through low-threshold Ca channels (T-type) with little effect on other noninactivating IBa including the nifedipine-sensitive one. The drug at 20 microM reduced transient IBa at a constant rate, -7.2% of the control per min, and abolished the current within 15 min. This implies a continuous accumulation of the drug in cell membranes probably because of its high lipophilicity (log P = 7.003). U-88779E also blocked Na and K currents but at a rate about 8 times slower than that observed with transient IBa. Further studies on interactions of the drug with T-channels revealed that the drug had no effect on the shape of current-voltage curve, activation and inactivation kinetics, and steady-state activation curve. The drug, however, induced a hyperpolarizing shift in steady-state inactivation curve and became more potent under conditions where the channels in inactivated states prevail. These observations are consistent with the view that U-88779E has a higher affinity to T-type channels in inactivated states than in resting or open states.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0022-3565
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
265
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
529-35
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8496804-Animals,
pubmed-meshheading:8496804-Barium,
pubmed-meshheading:8496804-Calcium Channel Blockers,
pubmed-meshheading:8496804-Cycloheptanes,
pubmed-meshheading:8496804-Ion Channel Gating,
pubmed-meshheading:8496804-Mice,
pubmed-meshheading:8496804-Neuroblastoma,
pubmed-meshheading:8496804-Piperazines,
pubmed-meshheading:8496804-Tumor Cells, Cultured
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Selective block of transient Ca channel current in mouse neuroblastoma cells by U-88779E.
|
| pubmed:affiliation |
Upjohn Company, CNS Disease Research, Kalamazoo, Michigan.
|
| pubmed:publicationType |
Journal Article
|