Stimulation of leukocyte adenyl cyclase by hydrocortisone and isoproterenol in asthmatic and nonasthmatic subjects

TLDR: The data suggest at least 2 mechanisms by which gluoocorticosteroids benefit asthmatic patients: Increased activity of adenyl cyclase, and Restoration ofAdenyl Cyclase responsiveness to catecholamines.

Abstract: To evaluate the theory of beta-adrenergic blockade in asthma, we measured the effects of hydrocortisone and isoproterenol on adenyl cyclase in peripheral blood leukocytes from asthmatic and nonasthmatic children and nonasthmatio adults. An intact cell method was used, allowing cells to incorporate 3 H-adenine and convert it to 3 H-adenosine triphosphate (ATP) during a 2 hour incubation. Experimental compounds were then added for a pulse exposure of 5 minutes. AdenyZ cyclase catalyzes the transformation of 3 H-ATP to 3 H-cyclic adenosine monophosphate (AMP), which was measured after chromatographic separation. To rule out effects on rate of cyclic AMP destruction, aminophylline was routinely added at 25 mM., a concentration which completely inhibited cyclic AMP phosphodiesterase. Hydrocortisone at 10 −6 M stimulated adenyl cyclase in leukocytes from all subjects by 24 to 85 per cent. Isoproterenol at 10 −6 M stimulated adenyl cyclase by 16 to 19 per cent in control subjects, but not in cells from asthmatic subjects, a finding which supports the beta-adrenergic blockade hypothesis. Children receiving glucocorticosteroid therapy showed a restoration of leukocyte adenyl cyclase responsiveness to Isoproterenol. No synergistic effects between the steroid and catecholamine were observed in vitro. The data suggest at least 2 mechanisms by which gluoocorticosteroids benefit asthmatic patients: (1) Increased activity of adenyl cyclase, and (2) Restoration of adenyl cyclase responsiveness to catecholamines.