Abnormal secretagogue-induced intracellular free Ca²⁺ regulation in cystic fibrosis nasal epithelial cells

These studies identify a further abnormality in cystic fibrosis (CF). The increase in intracellular free calcium contration ([Ca²⁺]_i,) after exposure to histamine and PGE₁, is demonstrated to be abnormally low in nasal cells, studied in short-term culture, from patients with CF compared with control subjects. [Ca²⁺]_i, is measured by using the Ca²⁺sensitive fluorescent dye fura-2 and a fluorescence microscope imaging system. The percentage of CF cells that increase [Ca²⁺]_i in response to histamine is decreased compared with controls, and, even in those CF cells that increase [Ca²⁺]_i, the magnitude of the increase in [Ca²⁺]_i in response to histamine is smaller than in controls. When exposed to PGE_i, a similar number of control and CF cells responded with an increase in [Ca²⁺]_i, but again the magnitude of the response was smaller in the CF ceHs. The mechanism of the PGE,-induced increase in [Ca²⁺]_i is not mediated by cAMP, since 8-bromo-cAMP failed to increase [Ca²⁺]_i in these cells. This abnormality in [Ca²⁺]_i) response did not apply to all secretagogues, with the response to carbachol being similar in CF and normal cells. How the abnormal CF gene product accounts for the abnor-mality hi intracellular Ca²⁺ response to some but not all secretagogues is unknown.