Linked Life Data

2467082

Source:http://linkedlifedata.com/resource/pubmed/id/2467082

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1989-5-3
pubmed:abstractText
To determine if species differences exist in myocardial response to 1,4-dihydropyridine (DHP) calcium channel blockers, the binding and pharmacologic responses of a series of DHP compounds were examined in both rat and rabbit myocardium. [3H]Nitrendipine was used to label specific binding sites in myocardial membrane particulates. The results of saturation binding experiments (n = 3) indicated no statistically significant difference in either Kd or Bmax between rat and rabbit myocardial membranes (0.19 +/- 0.02 nM and 157 +/- 29 fmol/mg protein in rat and 0.14 +/- 0.06 nM and 227 +/- 125 fmol/mg protein in rabbit). Furthermore, [3H]nitrendipine binding inhibition experiments using 12 unlabeled DHP analogues yielded Ki values for each compound that were almost identical in myocardium from rat and rabbit, resulting in an excellent 1:1 correlation when data for all of the compounds were compared (r = 0.997, p less than 0.001). The negative inotropic effect of five of these DHP compounds was studied in vitro in isolated right papillary muscles from rabbit and right ventricular strips from rat, and concentration required to displace 50% of ligand binding (IC50) values for inhibition of contraction were determined. The IC50 values were significantly greater in rat myocardium than in rabbit myocardium (p less than 0.003). Therefore, a significantly lower potency of DHP calcium channel blockers has been demonstrated in rat compared with rabbit myocardium, and this species difference cannot be explained by a difference in the DHP binding site. Rat myocardium differs from rabbit myocardium in a number of ways that may explain this lower potency.(ABSTRACT TRUNCATED AT 250 WORDS)
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
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
650-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Species differences in the negative inotropic response of 1,4-dihydropyridine calcium channel blockers in myocardium.
pubmed:affiliation
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't