IP3 receptor blockade fails to prevent intracellular Ca2+release by ET-1 and α-thrombin.

The effect of inositol 1,4,5-trisphosphate (IP3) receptor blockade on platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), endothelin-1 (ET-1), or α-thrombin receptor-mediated intracellular Ca2+([Formula: see text]) release was examined using fura 2 microspectrofluorometry in single Chinese hamster ovary cells and myoblasts. Blockade of the IP3receptor was achieved by microinjection of heparin or monoclonal antibody (MAb) 18A10 into the IP3type 1 receptor. Heparin completely inhibited[Formula: see text] release after flash photolysis with caged IP3 and after exposure to PDGF and FGF. In contrast, heparin failed to block[Formula: see text] release after α-thrombin and ET-1. After application of ligand, IP3 levels were five- to sevenfold higher for α-thrombin than for ET-1 or PDGF. IP3 levels after PDGF and ET-1 were comparable. Similar to heparin, MAb 18A10 blocked[Formula: see text] release after PDGF but failed to block [Formula: see text] release after ET-1 or α-thrombin. These data suggest that the mechanisms of[Formula: see text] release by tyrosine kinase and certain 7-transmembrane receptors may differ. Although both receptor types use the IP3-signaling system, the ET-1 and α-thrombin receptors may have a second, alternative mechanism for activating[Formula: see text] release.