Figure 1. Thromboxane A²(TXA²) signaling in Xenopus oocytes. (A) The signaling pathway linking TXA²receptor activation to chloride (Cl sup -) channel opening. The double line represents the cell membrane. Binding of the ligand to the receptor activates G proteins (exchanging GDP for GTP). G^qproteins activate phospholipase C (PLC-beta), which cleaves membrane phosphatidylinositolbisphosphate to inositol 1–4-5 trisphosphate (IP³) and diacylglycerol. IP³releases Ca²+ from intracellular stores, increasing intracellular Ca²+ concentration. Intracellular Ca²+ opens endogenous membrane Cl sup - channels, resulting in a Cl sup - flux (I^Cl[Ca]). Shaded arrows indicate the site of action of intermediates microinjected to activate intracellularly the signaling pathway. (B) Example of I^Cl(Ca) induced by U-46619 (10 sup -6 M) in oocyte-expressing TXA²receptors (screen capture using OoClamp [8]). The tracing shows a peak current of approximately 1.5 micro A. The method of integration is indicated: A horizontal cursor was placed at baseline and the segment between 9.4 and 35.4 s was highlighted (here indicated by arrows) and integrated. Charge movement is 4.3 micro C. (C) U-46619 activates TXA²receptors, recombinantly expressed in Xenopus oocytes, in a concentration-dependent manner. I^Cl(Ca) induced by 10 sup -3 M U-46619 (y^max, = 28) was 13.4 +/- 1.86 micro C. Curve fitting using the Hill equation revealed a half maximal effect concentration of 3.2 x 10 sup -7 +/- 1.1 x 10 sup -7 M and a Hill coefficient of 0.8 +/- 0.2 (n for each data point > 7).