The effect of procaterol treatment on beta-adrenergic bronchodilation and polymorphonuclear leukocyte responsiveness

Procaterol is a new and effective beta-adrenergic bronchodilator. To determine if procaterol administration could cause tachyphylaxis, airway and leukocyte beta-adrenergic function were monitored in 10 patients with asthma during two 4-wk, double-blind treatment periods, each preceded by a 2-wk beta-agonist washout. Treatment periods were randomized to placebo or procaterol (2 wk, 0.1 mg/day; 2 wk, 0.2 mg/day). At each 7 biweekly evaluations, the patient's cumulative bronchodilator dose-response to inhaled isoproterenol (0.1 to 0.64%) was measured, and venous blood was collected to quantitate, in vitro, the polymorphonuclear leukocyte (PMN) beta-adrenergic receptor's 125Iodo-cyanopindolol (125I-CYP) ligand binding and the PMN cyclic AMP response to isoproterenol and procaterol. Neither the airway nor leukocyte beta-adrenergic characteristics were changed during placebo treatment. Procaterol treatment reduced (p less than 0.05) the maximal 125I-CYP binding to PMN membranes but only during the initial 2 wk at low dosage. The percent PMN cyclic AMP increase to procaterol (10(-5) M) was also significantly (p less than 0.05) less during active treatment (141 +/- 40%) than during washout (256 +/- 24%) or placebo (257 +/- 32%). In contrast, procaterol treatment did not alter the acute isoproterenol bronchodilation response as measured by either the percent improvement in FEV1 or the dose required to produce 50% maximal bronchodilation. The duration of bronchodilation was not measured. Therefore, although procaterol therapy of asthma is associated with decreased PMN beta-adrenergic function, airway smooth muscle function appears not to be altered.