Tags

Type your tag names separated by a space and hit enter

Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents.
Arterioscler Thromb Vasc Biol. 1999 Sep; 19(9):2141-7.AT

Abstract

The cardioprotective effects of E-type prostaglandins (EPs) have been attributed to vasodilatation, inhibition of platelet and neutrophil function (EP(2) mediated), and an unknown "cytoprotective effect." We have hypothesized that selective activation of EP(3) receptors may cause cardioprotection. The prostanoid derivative ONO-AE-248 selectively binds to murine EP(3alpha) receptors expressed in Chinese hamster ovary (CHO) cells (K(i), 15 nmol/L) and prevents the rise in cAMP caused by forskolin in CHO cells (IC(50) approximately 1 nmol/L) in which the EP(3alpha) receptor had been expressed. In anesthetized rats subjected to regional myocardial ischemia for 25 or 45 minutes and 2 hours of reperfusion, infusion of ONO-AE-248 (5 microg kg(-1). min(-1) IV) caused a significant reduction in infarct size, from 60+/-3% (n=8) to 36+/-6% (n=7) and from 78+/-2% (n=11) to 58+/-4% (n=9), respectively. The reduction in infarct size caused by ONO-AE-248 in rats subjected to 25 minutes of ischemia and reperfusion was abolished by a selective inhibitor of ATP-sensitive potassium (K(ATP)) channels, 5-hydroxydecanoate (n=6), and the protein kinase C inhibitors staurosporine (n=6) and chelerythrine (n=6). In anesthetized rabbits subjected to coronary artery occlusion for 45 or 60 minutes and 2 hours of reperfusion, infusion of ONO-AE-248 (5 microg. kg(-1). min(-1) IV) caused a significant reduction in infarct size, from 61+/-2% (n=10) to 36+/-4% (n=8) and from 63+/-4% (n=7) to 42+/-4% (n=7), respectively. The reduction in infarct size caused by ONO-AE-248 in the rabbit was also abolished by 5-hydroxydecanoate. The cardioprotective effect of ONO-AE-248 in rats or rabbits was not associated with any hemodynamic effects. Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents by a mechanism(s) that may involve the activation of protein kinase C and the opening of K(ATP) channels.

Authors+Show Affiliations

William Harvey Research Institute, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10479656

Citation

Zacharowski, K, et al. "Selective Activation of the Prostanoid EP(3) Receptor Reduces Myocardial Infarct Size in Rodents." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 9, 1999, pp. 2141-7.
Zacharowski K, Olbrich A, Piper J, et al. Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents. Arterioscler Thromb Vasc Biol. 1999;19(9):2141-7.
Zacharowski, K., Olbrich, A., Piper, J., Hafner, G., Kondo, K., & Thiemermann, C. (1999). Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(9), 2141-7.
Zacharowski K, et al. Selective Activation of the Prostanoid EP(3) Receptor Reduces Myocardial Infarct Size in Rodents. Arterioscler Thromb Vasc Biol. 1999;19(9):2141-7. PubMed PMID: 10479656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents. AU - Zacharowski,K, AU - Olbrich,A, AU - Piper,J, AU - Hafner,G, AU - Kondo,K, AU - Thiemermann,C, PY - 1999/9/10/pubmed PY - 1999/9/10/medline PY - 1999/9/10/entrez SP - 2141 EP - 7 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 19 IS - 9 N2 - The cardioprotective effects of E-type prostaglandins (EPs) have been attributed to vasodilatation, inhibition of platelet and neutrophil function (EP(2) mediated), and an unknown "cytoprotective effect." We have hypothesized that selective activation of EP(3) receptors may cause cardioprotection. The prostanoid derivative ONO-AE-248 selectively binds to murine EP(3alpha) receptors expressed in Chinese hamster ovary (CHO) cells (K(i), 15 nmol/L) and prevents the rise in cAMP caused by forskolin in CHO cells (IC(50) approximately 1 nmol/L) in which the EP(3alpha) receptor had been expressed. In anesthetized rats subjected to regional myocardial ischemia for 25 or 45 minutes and 2 hours of reperfusion, infusion of ONO-AE-248 (5 microg kg(-1). min(-1) IV) caused a significant reduction in infarct size, from 60+/-3% (n=8) to 36+/-6% (n=7) and from 78+/-2% (n=11) to 58+/-4% (n=9), respectively. The reduction in infarct size caused by ONO-AE-248 in rats subjected to 25 minutes of ischemia and reperfusion was abolished by a selective inhibitor of ATP-sensitive potassium (K(ATP)) channels, 5-hydroxydecanoate (n=6), and the protein kinase C inhibitors staurosporine (n=6) and chelerythrine (n=6). In anesthetized rabbits subjected to coronary artery occlusion for 45 or 60 minutes and 2 hours of reperfusion, infusion of ONO-AE-248 (5 microg. kg(-1). min(-1) IV) caused a significant reduction in infarct size, from 61+/-2% (n=10) to 36+/-4% (n=8) and from 63+/-4% (n=7) to 42+/-4% (n=7), respectively. The reduction in infarct size caused by ONO-AE-248 in the rabbit was also abolished by 5-hydroxydecanoate. The cardioprotective effect of ONO-AE-248 in rats or rabbits was not associated with any hemodynamic effects. Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents by a mechanism(s) that may involve the activation of protein kinase C and the opening of K(ATP) channels. SN - 1079-5642 UR - https://www.unboundmedicine.com/medline/citation/10479656/Selective_activation_of_the_prostanoid_EP_3__receptor_reduces_myocardial_infarct_size_in_rodents_ L2 - https://www.ahajournals.org/doi/10.1161/01.atv.19.9.2141?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -