Characterization of signal transduction events stimulated by 8-epi-prostaglandin(PG)F2 alpha in rat aortic rings.
One of the most abundant F2 isoprostanes formed under pathological conditions is 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha), a potent vasoconstrictor. The purpose of this study was to determine the signal transduction events initiated by 8-epi-PGF2 alpha-induced vasoconstriction. Isolated arterial rings from male Sprague-Dawley rats were suspended in tissue baths containing Krebs-Henseleit salt solution, stretched to optimal resting tension and stimulated. 8-epi-PGF2 alpha induced concentration-dependent contractions in pulmonary arteries (EC50: 7.7 +/- 2.1 microM; n = 3) and aortas (EC50: 0.9 +/- 0.1 microM; n = 4) which were blocked by the TXA2 receptor antagonists SQ29548, L657925 and L657926. The contractile response to 8-epi-PGF2 alpha was significantly (*p < 0.05; n = 4) diminished by: 1) indomethacin and ibuprofen; 2) Ca++ free media; 3) verapamil, a voltage gated Ca++ channel blocker; 4) flunarizine, a T-type Ca++ channel blocker; and 5) calphostin C, a protein kinase C inhibitor. These data suggest that the contractile response to 8-epi-PGF2 alpha is: 1) mediated via activation of TXA2 receptors; 2) partially dependent on the synthesis and release of other cyclooxygenase derived products; 3) dependent on an influx of extracellular Ca++ possibly via Ca++ channels; and 4) may be PKC dependent.
Wagner
R S
RS
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202, USA.
Weare
C
C
Jin
N
N
Mohler
E R
ER
Rhoades
R A
RA
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D015220:Calcium Channels; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D017482:Receptors, Thromboxane; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D011493:Protein Kinase C; C058819:calphostin C; D002118:Calcium; D007213:Indomethacin