Linked Life Data

2450242

Source:http://linkedlifedata.com/resource/pubmed/id/2450242

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1988-4-18
pubmed:abstractText
The objective of the present study was to determine the time-courses for depression and recovery of calcium-mediated action potentials in canine Purkinje fibers following exposure to dihydropyridine (DHP) calcium channel antagonists and to determine if the reported discrepancy (up to 1,000 X) between I50 values for inducing physiologic effects in isolated tissues and the dissociation constant (Kd) for [3H]nitrendipine binding to membrane sites could be reduced when physiologic measurements were made under experimentally determined steady-state conditions. Changes in dV/dtmax of slow calcium-mediated action potentials (20 mM KCl, 10(-6) M isoproterenol) were recorded at 10-min intervals during exposure (2-4 h) to nifedipine, nitrendipine, and PY 108-068 (10(-9) M-4 X 10(-8) M). Time to steady state was slow, with half-life t1/2 values of 40 min (nifedipine), 84 min (nitrendipine), and 81 min (PY 108-068). Steady state I50 values for depressing dV/dtmax were 12.08 (nifedipine), 5.74 (nitrendipine), and 4.88 nM (PY 108-068). In isolated cardiac sarcolemma preparations (37 degrees C), these compounds competed for [3H]nitrendipine binding sites with Ki values of 8.1, 1.3, and 4.9 nM, respectively. These results show that attainment of steady-state depression of calcium channel function can be slow, but that the discrepancy between the physiologic data and the binding data is reduced significantly (less than 5 X) when physiologic measurements are made at steady state and binding studies are performed at 37 degrees C.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
707-15
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Relationship between steady-state depression of calcium-dependent action potentials and competition for binding sites by nifedipine, nitrendipine, and PY 108-068.
pubmed:affiliation
Department of Pharmacology, Medical University of South Carolina, Charleston 29425.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't