Alterations in Cyclic AMP Metabolism in Human Bronchial Asthma

Abstract

A B S T R A C T In an effort to clarify the basis for the reduced cyclic AMP response to catecholamines in leukocytes and lymphocytes from asthmatic donors the response of these cells to prostaglandins has been examined. Cells with an impaired beta adrenergic response had an essentially unaltered response to prostaglandin El (PGE1) indicating the presence of selective beta adrenergic blockade. In contrast to what was observed with cells from asthmatic individuals, in normal control leukocytes with reduced catecholamine responsiveness PGEi responses were usually reduced as well, suggesting a different mechanism. The excellent cyclic AMP response to PGE1 in cells from asthmatic donors would suggest that the defect in catecholamine responsiveness is at the level of the beta adrenergic receptor although a contributory role of altered substrate concentrations or increased phosphodiesterase activity is not formally excluded.