Beta adrenergic receptors in lymphocytes and granulocytes from patients with cystic fibrosis

Abstract

Intact lymphocytes from patients with cystic fibrosis (CF) produce significantly (P < 0.001) less adenosine 3':5' cyclic monophosphate (cAMP) than normal lymphocytes in response to isoproterenol (10-8-10-4 M), although the basal cAMP content and the response to prostaglandin E1 are normal. Obligate heterozygotes for CF have significantly (P < 0.005) reduced cAMP response to isoproterenol as well, suggesting a genetic component in the beta adrenergic deficiency in CF. The number of beta adrenergic receptors, as determined by equilibrium binding of [3H]dihydroalprenolol to lymphocyte particulates, is the same in normal lymphocytes (969 ± 165 receptors/cell) and lymphocytes from patients with CF (1,333 ± 263 receptors/cell). Binding properties of the receptor for both antagonist and agonist, as assessed by K(D) for dihydroalprenolol and K(i) for (-)-isoproterenol, are also normal in the CF lymphocytes. Similarly, in granulocytes from patients with CF, the cAMP response to isoproterenol (10-8-10-4 M) is significantly reduced compared with healthy controls (P < 0.03), as is the response of granulocytes from obligate heterozygotes (P < 0.05). Again, the basal cAMP levels and the response to prostaglandin E1 are normal. The number of beta adrenergic receptors, as determined by equilibrium binding of [3H]dihydroalprenolol to granulocyte particulates, was the same in normal (1,462 ± 249 receptors/cell) and CF (1,621 ± 221 receptors/cell) preparations. Binding properties of the receptor for both agonist and antagonist, as assessed by K(D) for dihydroalprenolol and K(i) for isoproterenol, are normal in CF granulocyte particulates. The lymphocyte and granulocyte beta adrenergic defect in CF cannot be explained by abnormalities of the beta adrenergic receptor or of adenylate cyclase itself. Receptor-cyclase coupling is the most likely site of the heritable beta adrenergic defect in CF.