Abstract
Thromboxane A2 (TXA2) is formed from the fatty acid precursor, arachidonic acid (AA), by the sequential actions of the enzymes cyclooxygenase and thromboxane synthetase1. It is readily generated by platelets and is a potent vasoconstrictor and inducer of platelet aggregation1,2. Studies in dogs show that the addition of AA to blood flowing through an incubation coil leads to production of TXA2, characterized by its instability and its ability to contract isolated strips of vascular tissue3. We now report that the formation of TXA2 from AA in blood can be inhibited by 1-benzylimidazole, a thromboxane synthetase inhibitor, and selectively by very low doses of indomethacin. In conditions of TXA2 inhibition, a vasodilator AA metabolite, presumably prostacyclin, is formed in the stomach. We show that TXA2 is a powerful gastric vasoconstrictor and can extensively damage the gastric mucosa, and suggest that it may be involved in the pathogenesis of certain ulcerative disorders of the stomach.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hamberg, M., Svensson, J. & Samuelsson, B. Proc. natn. Acad. Sci. U.S.A. 72, 2994–2998 (1975).
Moncada, S. et al. Prostaglandins 13, 611–618 (1977).
Mullane, K. M., Dusting, G. J., Salmon, J. A., Moncada, S. & Vane, J. R. Eur. J. Pharmac. 54, 217–218(1979).
Ritchie, W. P. Gastroenterology 68, 699–707 (1975).
Chignard, M. & Vargaftig, B. B. Eur. J. Pharmac. 38, 7–18 (1976).
Konturek, S. J., Mikos, E., Pawlik, W. & Walus, K. M. J. PhysioL, Lond. 286, 15–28 (1979).
Walus, K. M., Gustaw, P. & Konturek, S. J. Prostaglandins 20, 1089–1102 (1980).
Whittle, B. J. R., Moncada, S., Whiting, F. & Vane, J. R. Prostaglandins 19, 605–627 (1980).
Tai, H. H. & Yuan, B. Biochem. biophys. Acta 539, 162–172 (1978).
Harris, R. H. et al. Adv. Prostaglandin Thromboxane Res. 6, 457–461 (1980).
Moncada, S., Gryglewski, R. J., Bunting, S. & Vane, J. R. Nature 263, 663–665 (1976).
Vane, J. R. Nature new Biol. 231, 232–235 (1971).
Moncada, S. & Vane, J. R. New Engl. J. Med. 300, 1142–1147 (1979).
Whittle, B. J. R., Higgs, G. A., Eakins, K. E., Moncada, S. & Vane, J. R. Nature 284, 271–273 (1980).
Davenport, H. W. Gastroenterology 46, 245–253 (1964).
Whittle, B. J. R. Br. J. Pharmac. 60, 455–460 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Whittle, B., Kauffman, G. & Moncada, S. Vasoconstriction with thromboxane A2 induces ulceration of the gastric mucosa. Nature 292, 472–474 (1981). https://doi.org/10.1038/292472a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/292472a0
This article is cited by
-
Role of the NO/cGMP/KATP pathway in the protective effects of sildenafil against ethanol‐induced gastric damage in rats
British Journal of Pharmacology (2008)
-
Sildenafil prevents indomethacin‐induced gastropathy in rats: role of leukocyte adherence and gastric blood flow
British Journal of Pharmacology (2005)
-
Adventures and Excursions in Bioassay: The Stepping Stones to Prostacylin
Bioscience Reports (2004)
-
Thromboxanes: Synthase and receptors
Journal of Biomedical Science (1998)
-
Induction mechanism of small intestinal lesions caused by intravenous injection of endotoxin in rats
Surgery Today (1996)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.