Reduction of myocardial injury by the EP3 receptor agonist TEI-3356. Role of protein kinase C and of K(ATP)-channels.

Abstract

The effects of the prostanoid EP3 receptor agonist TEI-3356 on either protein kinase C or ATP-sensitive (K(ATP)) K+ channels and on the infarct size caused by regional myocardial ischaemia and reperfusion in the rat were investigated. Male Wistar rats (n = 72) were subjected to 25 min occlusion of the left anterior descending coronary artery followed by 2 h of reperfusion. TEI-3356 (1 microg/kg/min i.v., n = 6) caused a significant reduction in infarct size from 60+/-3% (control, n = 8) to 38+/-3% of the area at risk. Pretreatment of rats with 5-hydroxydecanoate (5 mg/kg i.v., n = 6), a specific inhibitor of K(ATP)-channels, attenuated the cardioprotective effects of TEI-3356. The reduction in infarct size afforded by TEI-3356 was also abolished by the protein kinase C inhibitors staurosporine (1 microg/kg i.v., n = 6) and chelerythrine (0.7 mg/kg i.v., n = 5). Thus, TEI-3356 reduces myocardial infarct size in the rat by a mechanism(s) which involves the activation of protein kinase C and the opening of K(ATP)-channels.

• Authors: K Zacharowski, A Olbrich, C Thiemermann
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 367 Issue 1 Pg. 33-9 (Feb 12 1999) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10082262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Anti-Arrhythmia Agents
• Benzophenanthridines
• Decanoic Acids
• Enzyme Inhibitors
• Hydroxy Acids
• Phenanthridines
• Potassium Channel Blockers
• Potassium Channels
• Ptger3 protein, rat
• Receptors, Prostaglandin E
• Receptors, Prostaglandin E, EP3 Subtype
• TEI 3356
• 5-hydroxydecanoic acid
• Adenosine Triphosphate
• Epoprostenol
• chelerythrine
• Protein Kinase C
• Staurosporine

Topics

• Adenosine Triphosphate (physiology)
• Alkaloids
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Benzophenanthridines
• Decanoic Acids (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Epoprostenol (analogs & derivatives, pharmacology, therapeutic use)
• Hemodynamics (drug effects)
• Hydroxy Acids (pharmacology)
• Male
• Myocardial Infarction (pathology, prevention & control)
• Myocardial Reperfusion
• Phenanthridines (pharmacology)
• Potassium Channel Blockers
• Potassium Channels (physiology)
• Protein Kinase C (antagonists & inhibitors, physiology)
• Rats
• Rats, Wistar
• Receptors, Prostaglandin E (agonists)
• Receptors, Prostaglandin E, EP3 Subtype
• Staurosporine (pharmacology)