Reduced responsiveness of adenylate cyclase in alveolar macrophages from patients with asthma.
Alveolar macrophages from patients with asthma accumulated less cyclic adenosine monophosphate when these macrophages were exposed to isobutyl methylxanthine, salbutamol, or prostaglandin E2, compared to cells from control subjects without asthma, and the degree of the hyporesponsiveness was related to the severity of asthma. In addition, a significantly lower adenylate cyclase activity was observed in crude membrane fractions of macrophages from the group with asthma in the presence of salbutamol and prostaglandin E2. The refractoriness observed in patients with asthma is thus not accounted for by a specific beta-adrenergic desensitization at the adenylate cyclase receptor level but should rather be explained by a cyclic adenosine monophosphate-dependent postreceptor mechanism.
Bachelet
M
M
Unité de Pharmacologie Cellulaire, Hôpital Rothschild, Paris, France.
Vincent
D
D
Havet
N
N
Marrash-Chahla
R
R
Pradalier
A
A
Dry
J
J
Vargaftig
B B
BB
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000032:analysis* / Q000187:drug effects; D000420:Albuterol / Q000494:pharmacology; D001249:Asthma / Q000201:enzymology* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002469:Cell Separation; D000242:Cyclic AMP / Q000032:analysis; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology
D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D000420:Albuterol; D015056:1-Methyl-3-isobutylxanthine