Airway effects of purine nucleosides and nucleotides and release with bronchial provocation in asthma.
Adenosine, AMP, and ADP all caused similar concentration-related bronchoconstriction when inhaled by patients with asthma, whereas the adenosine hydrolysis product inosine had no effect. Geometric mean provocation concentrations of adenosine AMP and ADP causing a 20% fall in forced expiratory volume in 1 s (PCf20) were 2.34, 4.27, and 2.19 mumol/ml and 40% fall in specific airway conductance (PCs40) 3.16, 5.01, and 2.0 mumol/ml. Bronchoconstriction was rapid in onset, reaching a maximum 2-5 min after a single inhalation of AMP. In 31 asthmatic subjects a positive correlation was established between airway responsiveness to histamine, as an index of non-specific responsiveness, and airway reactivity to adenosine (PCf20, r = 0.60; PCs40, r = 0.64; P less than 0.01). Following bronchial provocation with allergen in nine subjects, plasma levels of adenosine increased from a mean base line of 5.4 +/- 0.9 to 9.6 +/- 2.0 ng/ml at 15 min (P less than 0.01) in parallel with a fall in forced expiratory volume in 1 s. With methacholine provocation bronchoconstriction reached maximum 2-5 min postchallenge being followed by, but not accompanied by, significant increases in plasma levels of adenosine. These data suggest that adenosine is a specific bronchoconstrictor that may contribute to airflow obstruction in asthma.
D000241:Adenosine / Q000097:blood; D000244:Adenosine Diphosphate; D000249:Adenosine Monophosphate; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D007288:Inosine / Q000097:blood; D007700:Kinetics; D016210:Methacholine Chloride; D008688:Methacholine Compounds
D008688:Methacholine Compounds; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; D007288:Inosine; D000244:Adenosine Diphosphate; D006632:Histamine; D000241:Adenosine