Effects of some isoprostanes on the human umbilical artery in vitro.
1. Cumulative concentration-effect curves for the selective prostanoid TP receptor agonist U46619 and six isoprostanes were constructed in the human isolated umbilical artery. 2. All compounds except 8-iso-PGF3 alpha produced concentration-dependent contractions. The contractile response to the isoprostanes increased with each cumulative addition up to a point, after which subsequent addition reduced the contraction below the previous level. This 'downturn' in the concentration-effect curve did not occur with U46619. 3. The potencies of the compounds tested were as follows (pEC50 +/- s.e.mean): U46619, 6.7 +/- 0.2; 8-iso-PGE2, 6.5 +/- 0.1; 8-iso-PGF2 alpha, 5.8 +/- 0.2; 8-iso-PGE1, 5.4 +/- 0.1; 8-iso-PGF1 alpha, 5.0 +/- 0.1; 8-iso-PGF2 beta > 4.8; 8-iso-PGF3 alpha >> 4.8 (n = 4-17). Neither 8-iso-PGF2 beta nor 8-iso-PGF3 alpha at 44 microM had a significant effect on cumulative concentration-effect curves to U46619. 4. The selective TP receptor antagonist GR32191 (0.1 microM) caused rightward shifts in the concentration-effect curves to all the active compounds. pA2 values for GR32191 against U46619, 8-iso-PGE2, 8-iso-PGF2 alpha, 8-iso-PGE1 were 7.6 +/- 0.2, 9 +/- 1, 8.2 +/- 0.3 and 7.7 +/- 0.3, respectively (n = 4). 5. Neither N omega-nitro-L-arginine methyl ester (100 microM) nor the selective DP receptor antagonist BW A868C (50 nM) affected the complex concentration-effect curve to 8-iso-PGE2 (n = 3). 6. Stable contractions to U46619 (1-3 microM) were unaffected by anandamide at concentrations up to 60 microM.
Oliveira
L
L
Honours Biology & Pharmacology Programme, McMaster University, Hamilton, Ontario, Canada.
Stallwood
N A
NA
Crankshaw
D J
DJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D028421:Isoprostanes; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011247:Pregnancy; D011460:Prostaglandins F / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014469:Umbilical Arteries / Q000187:drug effects*
D001095:Arachidonic Acids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D006827:Hydantoins; D028421:Isoprostanes; D053284:Polyunsaturated Alkamides; D011460:Prostaglandins F; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; C058848:BW A868C; C037027:prostaglandin F2beta; C034238:prostaglandin F3alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015232:Dinoprostone; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester; C011987:8-isoprostaglandin E2