Stimulation of cyclic AMP production in human alveolar macrophages induced by inflammatory mediators and beta-sympathicomimetics.
We have investigated the effects of inflammatory mediators and beta-adrenoceptor agonists on the adenylyl cyclase responsiveness in alveolar macrophages from control subjects, patients suffering from chronic obstructive pulmonary disease (COPD) and asthmatics. Basal cyclic AMP (cAMP) levels in alveolar macrophages from COPD patients were significantly elevated (plus 42%) as compared to controls. In addition, the adenylyl cyclase responsiveness to prostaglandin E2, histamine and the beta-adrenoceptor agonist salbutamol was significantly impaired in alveolar macrophages from COPD patients and asthmatics. The lipid mediator platelet activating factor showed no effect on cAMP production in all three alveolar macrophage populations. Furthermore, the cAMP-enhancing effects of isoprenaline, salbutamol and histamine appeared to be mediated via beta 2-adrenoceptors and histamine H2-receptor subtypes respectively. Taken together, these data suggest an intrinsic desensitization phenomenon in alveolar macrophages from COPD patients and asthmatics.
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, Netherlands.
F D
FD
Beusenberg
J G
JG
Van Amsterdam
H C
HC
Hoogsteden
P R
PR
Hekking
J W
JW
Brouwers
H P
HP
Schermers
I L
IL
Bonta
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D001249:Asthma / Q000201:enzymology / Q000473:pathology; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000201:enzymology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000494:pharmacology; D012907:Smoking
D000318:Adrenergic beta-Agonists; D010972:Platelet Activating Factor; D006632:Histamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D007545:Isoproterenol; D000420:Albuterol