Linked Life Data

9774224

Source:http://linkedlifedata.com/resource/pubmed/id/9774224

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-12-22
pubmed:abstractText
Opioids directly decrease the contractile response of isolated ventricular cardiomyocytes to electrical stimulation. To investigate whether these effects are mediated via GTP-binding G(i/o) proteins we examined the influence of pertussis toxin on the effects of the kappa-opioid receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benz eneacetamide (U-50,488) methanesulphonate and on the as yet undescribed effects of the opioid peptide dynorphin A (1-8) on contraction. In isolated, electrically driven, rat ventricular cardiomyocytes both agents concentration dependently reduced cell shortening within 15 min, decreasing the contractile response by 79+/-4% (n=5) and 62+/-2% (n=6) of control values at maximal effective concentrations of 10 microM (U-50,488) and 1 microM [dynorphin A (1-8)], respectively. Pertussis toxin pre-treatment (200 ng/ml; 4.5-5 h) completely abolished the effects of U-50,488 and dynorphin A (1-8) on the contractile response, indicating that these effects are mediated via G(i/o) proteins. In addition, the non-selective opioid receptor antagonist (-)-naloxone and the kappa-opioid receptor antagonist nor-binaltorphimine antagonized the effects of U-50,488 and dynorphin A (1-8) on the contractile response. Furthermore, the mu- and delta-opioid receptor agonist (D-Ala2, D-Leu5)-enkephalin (DADLE) had no effects on contraction. These results indicate that the decrease in cell shortening is due to stimulation of kappa-opioid receptors. The direct effect of kappa-opioid receptor agonists on the contractile response thus represents an additional mechanism for decreasing cardiac contractility, besides the M-cholinoceptor- or adenosine receptor-mediated pathway. It is conceivable that increased release of endogenous dynorphins from the heart during hypoxia may protect the heart in a similar manner to adenosine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
358
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
360-6
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Diminution of contractile response by kappa-opioid receptor agonists in isolated rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G protein.
pubmed:affiliation
Rudolf-Buchheim-Institut für Pharmakologie der Justus-Liebig-Universität Giessen, Germany.
pubmed:publicationType
Journal Article