Characterization of prostanoid receptors mediating actions of the isoprostanes, 8-iso-PGE2 and 8-iso-PGF2[alpha], 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...

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Veröffentlicht in:British journal of pharmacology 2000-08, Vol.130 (8), p.1903
Hauptverfasser: Sametz, Wolfgang, Hennerbichler, Simone, Glaser, Sonja, Wintersteiger, Reinhold, Heinz, Juan
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container_issue 8
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container_title British journal of pharmacology
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creator Sametz, Wolfgang
Hennerbichler, Simone
Glaser, Sonja
Wintersteiger, Reinhold
Heinz, Juan
description 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.
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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. 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title Characterization of prostanoid receptors mediating actions of the isoprostanes, 8-iso-PGE2 and 8-iso-PGF2[alpha], in some isolated smooth muscle preparations
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