Thromboxane receptor secretion

Recently, it was shown that the thromboxane receptor itself is a substrate ofcGMP-PK and cAMP-PK in HEK293 cells, HEL cells, or with purified enzymes in vitro. Phosphorylation of its cytoplasmic carboxyterminal domain prevented the thromboxane receptor from coupling to and activating G-proteins [36, 37]. For intact platelets, TxA2 receptor phosphorylation has not yet been shown, however, it would provide another explanation for the inhibition of PLC activation and subsequent intracellular Ca2+ elevation and granule secretion in response to cyclic nucleotides. 

The formation of a platelet aggregate requires the recruitment of additional platelets from the blood stream to the injured vessel wall. This process is executed through a variety of diffusible mediators which act through G-protein-coupled receptors. The main mediators involved in this process are adenosine diphosphate (ADP), thromboxane A2 (TXA2), and thrombin (factor Ila). These mediators of the second phase of platelet activation are formed in different ways. While ADP is secreted from platelets by exocytosis, the release of TXA2 follows its new formation in activated platelets. Thrombin can be formed on the surface of activated platelets (see Fig. 2). 

Li Z, Zhang G, Le Breton GC, Gao X, Malik AB, Du X. Two waves of platelet secretion induced by thromboxane A2 receptor and a critical role for phosphoinositide 3-kinases. J Biol Chem 2003 278 30,725-30,73 I. 

Serotonin is a strong agonist for cat platelets and induces a biphasic aggregation response (Tschopp 1970). Response to serotonin is coupled to formation of thromboxane Bjand dense granule secretion. The serotonin receptor on cat platelets binds more serotonin than do platelets other species (Leysen et al. 1983). Epinephrine potentiates aggregation responses to other agonists. 

The contractile receptors are those that bind PGF, PCE, and thromboxane, btimulafion of these receptors provokes a burst of calcium ions and the contraction of smooth muscle The inhibitory receptor is the PGEj receptor Its stimulation results in a decline in cAMP levels and the consequent inhibition nerve activity, inhibition of gastric add secretion, and decline in water resorption (Kobayashid al., 1997). Iheso three functions provide a working guideline, but are not strict rules. 

Another study speculates on the attribution of diarrhoea induced by CPT-11 to effects on secretion. In this study, thromboxane synthase inhibitors such as indomethacin and a thromboxane A2 receptor blocker depressed the short-circuit current caused by CPT-11 [181]. This current depends on the presence of Cf ions and is considered to reflect the amount of secretion of these ions. Therefore, it was postulated that CPT-11 induces secretion of Cr ions mediated by eicosanoid and this secretion may be related to the occurrence of diarrhoea. 

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