![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 301, Issue 3, 1060-1066, June 2002
Asthma Research Group, Father Sean O'Sullivan Research Centre,
Firestone Institute for Respiratory Health, St. Joseph's Hospital,
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Although isoprostanes generally act on smooth muscle via
TXA2-selective prostanoid receptors (TPs), some suggest
other prostanoid receptors or possibly even a novel
isoprostane-selective receptor might be involved. We studied
contractions to several isoprostanes in porcine pulmonary vasculature
using organ bath techniques. 8-iso-prostaglandin E2
(PGE2) was the most potent and efficacious of the
isoprostanes, with a log EC50 of 
7.0 ± 0.2 in the
pulmonary artery and 6.8 ± 0.2 in the pulmonary vein. The
responses to all the isoprostanes were essentially completely blocked
by the TP receptor antagonist ICI 192605 [4(Z)-6-[(2,4,5-cis)2-(2-chlorophenyl)-4-(2-hydroxyphenyl)1,3-dioxan-5-yl]hexenoic acid], and the equilibrium dissociation constants for ICI 192605 competing with U46619 or 8-iso-PGE2 were both 
2
nM, indicating that isoprostane-evoked responses involve primarily TP
receptors. Only 8-iso-PGE2 was able to evoke substantial
contractions in the presence of ICI 192605 and only in the pulmonary
vein. The EC50 of these ICI 192605-insensitive responses
was 6.1 ± 0.2. Using a variety of prostanoid agonists, we found
the pulmonary vein lacked excitatory
PGF2
-selective prostanoid receptor (FP) or
PGD2-selective prostanoid receptor (DP) but expressed excitatory EP3 receptors. The ICI 192605-insensitive
responses to 8-iso-PGE2 were unaffected by the
EP1 antagonist SC-19220
[8-chloro-debenz[b,f][1,4]oxazepine-10(11H)-carboxy-(2-acetyl) hydrazine;
10
5 M] but were antagonized by the less selective
DP/EP1/EP2 antagonist AH6809
(6-isopropoxy-9-oxoxanthene-2-carboxylic acid; 105 M) or
by cyclopiazonic acid (105 M; depletes the internal
Ca2+ store). Our data indicate that, whereas
8-iso-PGE2 constricts pulmonary vasculature primarily
through TP receptors, a substantial portion of this response is also
directed through EP3 receptors or possibly a novel
isoprostane receptor.
This article has been cited by other articles:
|
|
 |
|
  L. J. Janssen Isoprostanes and Lung Vascular Pathology Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 383 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Seto, C. Hirota, S. Hirota, and L. J. Janssen E-Ring Isoprostanes Stimulate a Cl Conductance in Airway Epithelium via Prostaglandin E2-Selective Prostanoid Receptors Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 88 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Paredes, T. Tazzeo, and L. J. Janssen E-Ring Isoprostane Augments Cholinergic Neurotransmission in Bovine Trachealis via FP Prostanoid Receptors Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 739 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsumoto, M. Kakami, E. Noguchi, T. Kobayashi, and K. Kamata Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLETF rats, a model of Type 2 diabetes Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1480 - H1490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Cong, Z.-L. Xiao, P. Biancani, and J. Behar Prostaglandins mediate tonic contraction of the guinea pig and human gallbladder Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G409 - G418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ota, M. Aihara, T. Saeki, S. Narumiya, and M. Araie The Effects of Prostaglandin Analogues on Prostanoid EP1, EP2, and EP3 Receptor-Deficient Mice. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3395 - 3399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Losapio, R. S. Sprague, A. J. Lonigro, and A. H. Stephenson 5,6-EET-induced contraction of intralobar pulmonary arteries depends on the activation of Rho-kinase J Appl Physiol, October 1, 2005; 99(4): 1391 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Welch Effects of isoprostane on tubuloglomerular feedback: roles of TP receptors, NOS, and salt intake Am J Physiol Renal Physiol, April 1, 2005; 288(4): F757 - F762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. MONTUSCHI, P. J. BARNES, and L. J. ROBERTS II Isoprostanes: markers and mediators of oxidative stress FASEB J, December 1, 2004; 18(15): 1791 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Catalli and L. J. Janssen Augmentation of bovine airway smooth muscle responsiveness to carbachol, KCl, and histamine by the isoprostane 8-iso-PGE2 Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L1035 - L1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Cracowski and O. Ormezzano Isoprostanes, emerging biomarkers and potential mediators in cardiovascular diseases Eur. Heart J., October 1, 2004; 25(19): 1675 - 1678. [Full Text] [PDF]
|
|
|
|
 |
|
 J-L Cracowski The putative role of isoprostanes in human cardiovascular physiology and disease: following the fingerprints Heart, August 1, 2003; 89(8): 821 - 822. [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Cowley Isoprostane-Mediated Secretion from Human Airway Epithelial Cells Mol. Pharmacol., August 1, 2003; 64(2): 298 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, T. Tazzeo, S. Hirota, and L. J. Janssen Vasodilatory and Electrophysiological Actions of 8-iso-Prostaglandin E2 in Porcine Coronary Artery J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1054 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Weber and L. M. Markillie Regulation of Activator Protein-1 by 8-iso-Prostaglandin E2 in a Thromboxane A2 Receptor-Dependent and -Independent Manner Mol. Pharmacol., May 1, 2003; 63(5): 1075 - 1081. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
