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Chemical Compound Review:

STA 2 (Z)-7-[(1S,2R,5S)-3-[(E,3S)- 3-hydroxyoct-1...

Synonyms: ONO 11113, ONO 11,113, 89617-02-7, 111200-21-6, 9,11-Epithio-11,12-methano-TXA2, ...

Coe, Y. et al., Nishiye, E. et al., Nakahata, N. et al., Liu, Y.A. et al., Halushka, P.V. et al., et al.

Coceani, Liu, Seidlitz, Kelsey, Kuwaki, Ackerley, Yanagisawa,

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Disease relevance of STA2

Pulmonary hypertension being elicited by infusion of the thromboxane A(2) analog, 9,11-epithio-11,12-methano-thromboxane A(2) (ONO-11113) was instead not amenable to ET(A)R inhibition [1].
Blood levels of ET-1, which rose with hypoxia but not ONO-11113 treatment, were not changed by either antagonist [1].
9,11-Epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of thromboxane A2 (TXA2), activated GTPase in membranes derived from human astrocytoma cells, rabbit astrocytes and human platelets with different potencies [2].

High impact information on STA2

Co-administration of glucagon did not potentiate Ca2+ influx by ONO-11113, but the action of ONO-11113 was inhibited (50%) by a few minutes' prior administration of 10 nM-vasopressin [3].
These agonists were equipotent in the canine platelet but ONO-11113 was more potent in the saphenous vein [4].
Effects of high K+, acetylcholine (ACh), 9,11-epithio-11,12-methanothromboxane A2 (STA2), thrombin and endothelin were investigated on smooth muscles of the guinea pig coronary artery in intact and endothelium-denuded tissues [5].
ET(A) -/- DA, unlike ET(A) +/+ DA, contracted marginally to O(2) and ET-1 but responded to ONO-11113 [6].
Stimulation of the COS-7 cells with the TXA2 receptor agonist, ONO 11113 resulted in a significant increase in cAMP formation that was blocked by a receptor antagonist [7].

Biological context of STA2

Polymyxin B also decreased the IC50 values of the TXA2/PGH2 agonist ONO 11113 from 75 +/- 11 nM to 38 +/- 2.5 nM and the TXA2/PGH2 receptor antagonist SQ29548 from 60 +/- 14 nM to 20 +/- 2.3 nM [8].

Associations of STA2 with other chemical compounds

The same arteries contracted strongly to a thromboxane A(2) analogue (ONO-11113, 0.1 microM) and ET-1 (10 nM), while their contraction to activating solution (5 mM Ca(2+) in K(+)-Krebs solution) was small and variable [9].

Analytical, diagnostic and therapeutic context of STA2

Consistent with findings in vivo, when using isolated pulmonary resistance arteries from term fetal lamb, PD 156707 curtailed the hypoxia- but not the ONO-11113-induced constriction [1].

References

The endothelin A receptor antagonists PD 156707 (CI-1020) and PD 180988 (CI-1034) reverse the hypoxic pulmonary vasoconstriction in the perinatal lamb. Coe, Y., Haleen, S.J., Welch, K.M., Liu, Y.A., Coceani, F. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
Gq/11 communicates with thromboxane A2 receptors in human astrocytoma cells, rabbit astrocytes and human platelets. Nakahata, N., Miyamoto, A., Ohkubo, S., Ishimoto, H., Sakai, K., Nakanishi, H., Ohshika, H., Ohizumi, Y. Res. Commun. Mol. Pathol. Pharmacol. (1995) [Pubmed]
Prostaglandin F2 alpha and the thromboxane A2 analogue ONO-11113 stimulate Ca2+ fluxes and other physiological responses in rat liver. Further evidence that prostanoids may be involved in the action of arachidonic acid and platelet-activating factor. Altin, J.G., Bygrave, F.L. Biochem. J. (1988) [Pubmed]
Pharmacologic characterization of human and canine thromboxane A2/prostaglandin H2 receptors in platelets and blood vessels: evidence for different receptors. Mais, D.E., Saussy, D.L., Chaikhouni, A., Kochel, P.J., Knapp, D.R., Hamanaka, N., Halushka, P.V. J. Pharmacol. Exp. Ther. (1985) [Pubmed]
Mechanical and electrical properties of smooth muscle cells and their regulations by endothelium-derived factors in the guinea pig coronary artery. Nishiye, E., Chen, G.F., Hirose, T., Kuriyama, H. Jpn. J. Pharmacol. (1990) [Pubmed]
Endothelin A receptor is necessary for O(2) constriction but not closure of ductus arteriosus. Coceani, F., Liu, Y., Seidlitz, E., Kelsey, L., Kuwaki, T., Ackerley, C., Yanagisawa, M. Am. J. Physiol. (1999) [Pubmed]
Cloning and characterization of an endogenous COS-7 cell thromboxane A2 receptor. Becker, K.P., Ullian, M., Halushka, P.V. Biochim. Biophys. Acta (1998) [Pubmed]
Polymyxin B increases TXA2/PGH2 agonist and antagonist affinities in human platelet membranes. Halushka, P.V., Boehm, A., Mais, D.E. Eicosanoids (1988) [Pubmed]
Contractile and relaxing mechanisms in pulmonary resistance arteries of the preterm fetal lamb. Liu, Y.A., Theis, J.G., Coceani, F. Biol. Neonate (2000) [Pubmed]

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