Occupation of the prostaglandin E2-type 1 receptor increases rat atrial contractility via a Y-27632-sensitive pathway.
This study investigated whether rat left atria (LA) contain the prostaglandin E2 type 1 receptor (EP1) and whether EP1 occupation induces positive inotropic responses in superfused LA. Western analysis demonstrated that LA contain EP1 and the EP1 splice variant. Exposing isolated, superfused LA to 17-phenyl trinor PGE2, an EP1 agonist, increased isometric contractile force and its corresponding dF/dTs to approximately 70% of the isoproterenol maximum with an EC50 of approximately 80 nM. In contrast, agonists for EP2, EP3, and EP4 caused little change in LA function. While the EP1 antagonists SC-51089 and SC-19220 blocked 17-phenyl trinor PGE2-induced inotropy, neither prazosin, nadolol, atropine nor EI-283, a pan-specific protein kinase C inhibitor, affected 17-phenyl trinor PGE2-induced inotropy. However, Y-27632 and HA-1077, inhibitors of rho A-activated protein kinases, prevented and reversed the increase in LA contractility that occurred in the presence of 17-phenyl trinor PGE2. Thus, atria contain EP1 and EP1 occupation increases LA contractility via a pathway sensitive to inhibitors of rho A-activated protein kinases.
Wolkowicz
Paul E
PE
Department of Medicine, University of Alabama at Birmingham, 35294, USA. wolk@uab.edu
Ku
David D
DD
Grenett
Heman E
HE
Urthaler
Ferdinand
F
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D016279:Atrial Function, Left / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D054460:rho-Associated Kinases
D018674:Adrenergic Antagonists; D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; C545637:Ptger1 protein, rat; D011725:Pyridines; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; C049347:fasudil