ADENYLATE-CYCLASE IN LEUKOCYTES FROM PATIENTS WITH CYSTIC-FIBROSIS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 96  (1) , 75-84
Abstract
Lymphocytes from patients with cystic fibrosis produce significantly less c[cyclic]AMP in response to .beta.-adrenergic stimulation than do cells from healthy persons (P < 0.0005), or patients with bronchiectasis (P < 0.005). Adenylate cyclase in the basal state or stimulated by GMPPNP [guanyl-5''-yl imidodiphosphate] or PGE1 [prostaglandin E-1] is normal, but isoproterenol-stimulated adenylate cyclase activity is significantly (P < 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 < 0.0005), or subjects with bronchiectasis (P < 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 < 0.05) reduced compared to normal when stimulated by isoproterenol. The defect is apparently unrelated to adenylate cyclase itself, or to availability of substrate or cofactor to adenylate cyclase. The defect may be indicative of a more generalized membrane defect in cystic fibrosis.