Roles of thromboxanes in gastrointestinal physiopathology.

Prostaglandin (PG) precursors can be converted into many related substances with diverse biological activities. Products formed from arachidonate include thromboxane A2, which is a potent platelet aggregator and vasoconstrictor. Mucosa and muscle from human stomach, ileum and colon yield substantial amounts of this substance, and thromboxane A2 is also formed in the alimentary tract of other species. Injection of arachidonic acid or a stable thromboxane A2-mimetic (U-46619) into the arterial blood supplying dog stomach causes mucosal ischaemia. The ensuing necrosis that occurs with arachidonic acid when the mucosa is bathed with HCl and taurocholic acid can be prevented by a thromboxane synthetase inhibitor. Isolated gastrointestinal muscle contracts to low amounts of the thromboxane A2-mimetic U-46619, some human tissues being sensitive to less than 1pg/ml. These findings constitute a rational basis for examining thromboxane synthetase inhibitors in peptic ulceration and smooth muscle spasm. Unlike cyclo-oxygenase inhibitors, thromboxane synthetase inhibitors spare, or even increase, the formation of prostanoids with actions opposite to those of thromboxane A2.