Different receptors use inositol trisphosphate to mobilize Ca2+ from different intracellular pools

In cells expressing different receptors linked to Ins(1,4,5)P₃ formation, maximal stimulation of any one of them often releases all the Ins(1,4,5)P₃-sensitive Ca²⁺ stores, suggesting that Ins(1,4,5)P₃ is used similarly by many receptors. In single HEK-293 cells, ATP and carbamylcholine (CCh) stimulated Ca²⁺ release from intracellular stores via a pathway that was entirely dependent on Ins(1,4,5)P₃. After stimulation with maximal concentrations of ATP or CCh in Ca²⁺-free medium, there was no response to a second stimulation with the same agonist, indicating that each agonist had emptied the Ins(1,4,5)P₃-sensitive stores to which it had access. However, the Ca²⁺ release evoked by the second agonist was unaffected by prior stimulation with the first. We conclude that Ins(1,4,5)P₃ mediates the effects of both receptors, but Ins(1,4,5)P₃ is more versatile than hitherto supposed, because the spatial organization of the signalling pathways apparently allows Ins(1,4,5)P₃ made in response to each agonist to interact with different Ins(1,4,5)P₃ receptors.