Adenylate cyclase in leukocytes from patients with cystic fibrosis

Lymphocytes from patients with cystic fibrosis produce significantly less cAMP in response to beta-adrenergic stimulation than do cells from healthy persons (p less than 0.0005) or patients with bronchiectasis (p less than 0.005). Adenylate cyclase in the basal state or stimulated by GMPPNP or PGE1 is normal, but isoproterenol-stimulated adenylate cyclase activity is significantly (p less than 0.005) reduced in lymphocyte membrane preparations from patients with cystic fibrosis. Granulocytes from patients with cystic fibrosis also produce significantly less cAMP in response to beta-adrenergic stimulation than do cells from healthy subjects (p less than 0.0005) or subjects with bronchiectasis (p less than 0.05). Adenylate cyclase activity in granulocyte homogenates from patients with cystic fibrosis is normal in the basal state or when stimulated by GMPPNP or PGE1 but is significantly (p less than 0.05) reduced compared to normal when stimulated by isoproterenol. These data suggest that the defect is not related to adenylate cyclase itself or to availability of substrate or cofactor to adenylate cyclase, and they may be indicative of a more generalized membrane defect in cystic fibrosis.