Hormone-sensitive adenylate cyclase system in lymphocytes from asthmatic patients: possible defects at the postreceptor sites.

To clarify the mechanism of beta adrenergic hyporesponsiveness, which is related to bronchial hypersensitivity in asthmatic patients, cAMP responsiveness in peripheral lymphocytes was examined. The cAMP response to isoproterenol significantly decreased in the lymphocytes from asthmatics compared with those from healthy subjects. In contrast, the responses to GTP, Gpp(NH)p (a GTP analogue), sodium fluoride, and forskolin (a direct stimulator of the catalytic unit) were similar between the two groups. These results suggest that impairment of the stimulatory GTP binding protein or the catalytic unit is not the major cause of beta adrenergic hyporesponsiveness in asthma, and that hyporesponsiveness may be due to other mechanisms in the hormone-sensitive adenylate cyclase system.