Ca2+ entry but not Ca2+ release is necessary for desensitization of ETA receptors in airway epithelial cells

Ca2+ transients evoked by endothelin-1 (ET-1) were measured in single cells of a human tracheal epithelial cell line using the fluorescent Ca2+ indica tor fura-2. In line with a previous study, a single exposure to ET-1 (10 nM ) for 10-20 s resulted in a long-lasting desensitization to a subsequent ch allenge by the peptide, without affecting sensitivity to agonists For other Ca2+-mobilizing receptors such as P-2y or H-1, respectively. In the absence of extracellular Ca2+ ET-1 elicited a Ca2+ signal of compara ble amplitude as in the presence of extracellular Ca2+ but of shorter durat ion. Exposure to ET-1 in the absence of Ca2+ caused significantly less dese nsitization. Inhibition of the Ca2+ entry component of the Ca2+ transient by means of SK &F 96365, an inhibitor of Ca2+ entry, had effects comparable to Ca2+ remova l. The Ca2+ transient was shortened but not significantly reduced in amplit ude, and desensitization was reduced in the presence of the compound. These data demonstrate that desensitization of ETA receptors (ETAR) is promoted by transmembrane Ca2+ entry but not by Ca2+ release.