Characterization of prostanoid receptors mediating actions of the isoprostanes, 8-iso-PGE(2) and 8-iso-PGF(2alpha), in some isolated smooth muscle preparations.
We investigated the contracting actions of the isoprostanes (isoPs), 8-iso-prostaglandin (PG) F(2alpha) and 8-iso-PGE(2), in comparison to the effects of the thromboxane (TX) A(2)-mimetic U 46619 and the traditional prostaglandin PGE(2) in the isolated rat aorta, isolated rat gastric fundus and the isolated guinea-pig ileum. U 46619 and 8-iso-PGF(2alpha) caused contractions in the rat aorta and rat gastric fundus in a concentration-dependent manner, whereas these agonists showed no effects in the guinea-pig ileum. However, 8-iso-PGE(2) and PGE(2) caused contractions in all isolated organs used. The prostanoid TP-receptor antagonist SQ 29,548 (10 nM) significantly antagonized vasoconstrictions induced by the agonists used in the rat aorta. SQ 29,548 at a final concentration of 3 microM, but not at lower concentrations, significantly inhibited contractions induced by U 46619, 8-iso-PGF(2alpha) and 8-iso-PGE(2) in the rat fundus. Responses to PGE(2) were unchanged. The prostanoid EP(1)-receptor antagonist SC 51089 (3 microM) significantly inhibited contractions induced by 8-iso-PGE(2) and PGE(2) in the rat fundus and in the guinea-pig ileum. SC 51089 had no effect on responses to any of the agonists tested. Our results show that 8-iso-PGE(2), in contrast to 8-iso-PGF(2alpha), can also cause contractions by activation of the EP(1)-receptors in the rat gastric fundus and the guinea-pig ileum. The findings of the present study do not support the existence of a unique isoP-receptor in the tissues used.
Sametz
W
W
Department of Biomedical Research, University of Graz, Roseggerweg 48, A-8036 Graz, Austria.
Hennerbichler
S
S
Glaser
S
S
Wintersteiger
R
R
Juan
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006834:Hydrazines / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D028421:Isoprostanes; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010077:Oxazepines / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors; D058306:Receptors, Prostaglandin E, EP1 Subtype; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004146:Dioxanes; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D028421:Isoprostanes; D010077:Oxazepines; D011448:Prostaglandin Antagonists; C545637:Ptger1 protein, rat; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C057498:ICI 192605; C086836:SC 51089; C075750:8-epi-prostaglandin F2alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost; D015232:Dinoprostone; C011987:8-isoprostaglandin E2