Comparisons of the effects of fenoterol on PCA and histamine skin test in rats.

medication was discontinued. However, there was a suggestion that the recovery period might be somewhat longer in asthmatic adults than in children. To determine whether the effects of oral sympathomim&ic agents on leukocyte cyclic AMP responses might differ in normal and asthmatic subjects, a comparison was made of the effects of short-term treatment with ephedrine in the two groups. All subjects were treated with ephedrine 25 mg four times daily for seven days; asthmatic patients were also given one week of placebo treatment in randomized order. Results obtained during the mntrol and placebo periods again demonstrated that when asthmatic patients were not receiving treatment with adrenergic medications, the leukocyte cyclic AMP measurements were similar to those of normal subjects. Treatment with ephedrine for seven days was associated with reduction in the leukocyte cyclic AMP responses to adrenergic stimulation in both groups. However, in normal subjects the changes in respofise barely achieved significance (P <.05 by comparison of paired data), whereas m asthmatic patients, the changes were highly significant (P <.001). Comparison of the mean results in the two p u p s also demonstrated that the reduction of response after identical therapy witb ephedrine was sigdcantly greater in asthmatic subfects (P <.01). In the above study after collection of the initial specimens, subjects were given UX) rg of epinephrine by subcutaneous injection and a second sample was obtained two hours later. In both groups, leukocytes obtained after treatment with epinephrine were virtuany unresponsive to further adrenergic stimulation in d r o . There were no differences in the responses of specimens obtained during the control and ephedrine periods. However, in asthmatic subjects, the reduction of response after seven days of treatment with ephedrine was comparable to that observed after administration of epinephrine ( J Cyclic Nuc Res, 3:439, 1977 The results of our studies indicate that the altered leukocyte responses which have been observed in asthmatic subjects are largely due to the effects of recent therapy with adrenergic medications rather than the underlying disease. The similarity of results after treatment with several different medications suggests that exposure to any beta-adrenergic agonist is followed by suppression of the leukocyte responses to further adrenergic stimulation. The change in response can be demonstrated in both normal and asthmatic subjects within two hours after administration of an intense adrenergic stimulus and persists for a relatively long time. After administration of smaller amounts of medication the suppression of leukocyte response appears to be greater in asthmatic patients than in normal subjecb, suggesting a possible difference in the susceptibility of the two p u p s to suppression or in the time required for recovery of normal response. This may indicate a M e r ence in the number or availability of cellular betaadrenergic receptors in the two groups. Comparisons of the Effects of Fenoterol on PCA and Histamine Skin Test in Rats