Linked Life Data

11369032

Source:http://linkedlifedata.com/resource/pubmed/id/11369032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-5-22
pubmed:abstractText
Acidic extracellular pH reduced high-voltage-activated (HVA) currents in freshly isolated cortical pyramidal neurones of adult rats, shifting activation to more positive voltages (V(1/2)=-18 mV at pH 7.4, -11 mV at pH 6.4). Sipatrigine inhibited HVA currents, with decreasing potency at acidic pH (IC(50) 8 microM at pH 7.4, 19 microM at pH 6.4) but the degree of maximal inhibition was >80% in all cases (pH 6.4-8.0). Sipatrigine has two basic groups (pK(A) values 4.2, 7.7) and at pH 7.4 is 68% in monovalent cationic form and 32% uncharged. From simple binding theory, the pH dependence of sipatrigine inhibition indicates a protonated group with pK(A) 6.6. Sipatrigine (50 microM) shifted the voltage dependence of channel activation at pH 7.4 (-7.6 mV shift) but not at pH 6.4. Lamotrigine has one basic site (pK(A) 5.5) and inhibited 34% of the HVA current, with similar potency over the pH range 6.4--7.4 (IC(50) 7.5--9 microM). These data suggest that the sipatrigine binding site on HVA calcium channels binds both cationic and neutral forms of sipatrigine, interacts with a group with pK(A)=6.6 and with the channel activation process, and differs from that for lamotrigine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
784-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Effects of extracellular pH on the interaction of sipatrigine and lamotrigine with high-voltage-activated (HVA) calcium channels in dissociated neurones of rat cortex.
pubmed:affiliation
Section of Pharmacology, School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't