Secretion

Figure 2.* Signaling Pathways for TXA2 and Thrombin Receptors

A comprehensive model for the role of G proteins in agonist binding to TP receptors, similar to those developed for other GPCR (See 125, 151 for reviews), has not been presented. However, the allosteric ternary complex model (also called extended ternary complex model), formulated on the basis of data obtained from the study of p-adrenergic receptors (152, 153), may be applicable. The allosteric ternary complex model predicts that these receptors exist in active (R*) and inactive (R) equilibrium states governed by an isomerization constant. In this model G proteins bind only to R* resulting in R*G, but agonist binding 1) shifts the R to R* equilibrium by an allosteric constant and 2) affects R*G stability by a second allosteric constant. The allosteric constants affect agonist efficacy and the apparent dissociation constants of any ligand. Therefore binding analysis of receptor function necessitates an evaluation of receptors in terms of their spontaneous isomerization, ligand dependent allosteric constant and ligand G protein allosteric constant. This type of evaluation has not been performed for TP receptors.

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