Beta-adrenergic receptors and m-cholinergic receptors in human lung. Findings following in vivo and in vitro exposure to the beta-adrenergic receptor agonist, terbutaline.
In order to investigate whether treatment with terbutaline (1 mg subcutaneously) in patients with bronchial obstruction is accompanied by changes in the densities of receptors of the autonomic nervous system, beta-adrenergic receptors or m-cholinergic receptors were measured in membrance preparations of human peripheral lung tissue from patients undergoing lung resection for bronchial carcinoma. The density of beta-adrenergic receptors and mononuclear leukocytes (MNLs) of treated and untreated patients and beta-adrenergic receptors and m-cholinergic receptors in lung strips from the same patients exposed to terbutaline in vitro were studied for comparison. In patients, treatment with terbutaline did not have any effect on human lung beta-adrenergic receptors and m-cholinergic receptors, whereas a 57 percent decline was measured in the number of beta-receptors on MNLs of the very same patients. In contrast, in vitro exposure of human peripheral lung strips to terbutaline (100 mumol/L for 36 hours) evoked a time-dependent and concentration-dependent decline of 46 percent in beta-adrenergic receptors. Again, there was no change in the number of m-cholinergic receptors. The antagonist affinities, as judged from the KD values, did not differ under either condition. We concluded that lung beta-adrenergic receptors are subject to down-regulation when exposed to agonists in vitro. This down-regulation in the human lung is not accompanied by alterations in m-cholinergic receptors. Down-regulation of beta-adrenergic receptors or up-regulation of m-cholinergic receptors appears not to play a role in the proposed tolerance to beta-adrenergic receptor agonist treatment in clinical situations. The reduction of beta-adrenergic receptors in MNLs provides evidence that treatment with terbutaline was sufficient to affect beta-adrenergic receptors in vivo in certain cell types but also shows that alterations in blood cells do not necessarily reflect the situation in the lung.
Böhm
M
M
Medizinische Klinik I, University of Munich, Germany.
Gengenbach
S
S
Hauck
R W
RW
Sunder-Plassmann
L
L
Erdmann
E
E
D000368:Aged; D000369:Aged, 80 and over; D000402:Airway Obstruction / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008168:Lung / Q000737:chemistry* / Q000378:metabolism; D008875:Middle Aged; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000032:analysis* / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology*
D010276:Parasympatholytics; D010880:Piperidines; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D013726:Terbutaline; C048593:otenzepad