RGD Reference Report - Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat. - Rat Genome Database

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Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat.

Authors: Zacharowski, K  Olbrich, A  Otto, M  Hafner, G  Thiemermann, C 
Citation: Zacharowski K, etal., Br J Pharmacol. 1999 Feb;126(4):849-58.
RGD ID: 10043342
Pubmed: PMID:10193764   (View Abstract at PubMed)
PMCID: PMC1571228   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.bjp.0702348   (Journal Full-text)

1. This study investigates the effects of two agonists of the prostanoid EP3-receptor (M&B 28767 and GR 63799X) on the infarct size caused by regional myocardial ischaemia and reperfusion in the anaesthetized rat. 2. One hundred and sixty-seven, male Wistar rats were anaesthetized (thiopentone, 120 mg kg(-1) i.p.), ventilated (8-10 ml kg(-1), 70 strokes min(-1), inspiratory oxygen concentration: 30%; PEEP: 1-2 mmHg) and subjected to occlusion of the left anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min) followed by reperfusion (2 h). Infarct size was determined by staining of viable myocardium with a tetrazolium stain (NBT), histological evaluation by light and electron microscopy and determination of the plasma levels of cardiac troponin T. 3. M&B 28767 (0.5 microg kg(-1) min(-1), i.v., n=7) or GR 63799X (3 microg kg(-1) min(-1), i.v., n=7) caused significant reductions in infarct size from 60+/-3% (25 min ischaemia and 2 h reperfusion; saline-control, n=8) to 39+/-6 and 38+/-4% of the area at risk, without causing a significant fall in blood pressure. Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP-sensitive potassium channels, attenuated the cardioprotective effects of both EP3-receptor agonists. The reduction in infarct size afforded by M&B 28767 was also abolished by glibenclamide and the protein kinase C (PKC) inhibitors staurosporine and chelerythrine. 4. Thus, M&B 28767 and GR 63799X reduce myocardial infarct size in the rat by a mechanism(s) which involves the activation of PKC and the opening of ATP-sensitive potassium channels.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Myocardial Reperfusion Injury treatmentISOPtger3 (Rattus norvegicus)10043342; 10043342 RGD 
Myocardial Reperfusion Injury treatmentIMP 10043342 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptger3  (prostaglandin E receptor 3)

Genes (Mus musculus)
Ptger3  (prostaglandin E receptor 3 (subtype EP3))

Genes (Homo sapiens)
PTGER3  (prostaglandin E receptor 3)


Additional Information