tei-3356 and chelerythrine

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.

Topics: Adenosine Triphosphate; Alkaloids; Animals; Anti-Arrhythmia Agents; Benzophenanthridines; Decanoic Acids; Enzyme Inhibitors; Epoprostenol; Hemodynamics; Hydroxy Acids; Male; Myocardial Infarction; Myocardial Reperfusion; Phenanthridines; Potassium Channel Blockers; Potassium Channels; Protein Kinase C; Rats; Rats, Wistar; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP3 Subtype; Staurosporine