Effects of in vitro mast cell degranulation on human lung beta-receptor binding parameters.
BACKGROUND
Numerous studies have demonstrated that subjects with allergic asthma have beta-adrenergic hyporesponsiveness, predisposing these individuals toward bronchospasm, mucous production, and mast cell degranulation. Since sympathetic innervation of the human respiratory tract is sparse, reduced beta-responsiveness probably results from alterations at or beyond the receptor level.


OBJECTIVE
We therefore examined whether anaphylaxis of human lung tissue acutely modulated the human lung beta-receptor system in ways that might lead to decreased beta-adrenergic responsiveness.


METHODS
Fresh thoracotomy peripheral lung samples from 26 patients were incubated with (anaphylaxis) or without (control) anti-IgE (1:100) for up to 90 minutes and histamine release was documented. Lung fragments were quick frozen at various times after anti-IgE for analyses of beta-receptor binding parameters. Antagonist Kd (dissociation constant) and receptor concentration values were determined using (-)[125I]pindolol and agonist IC50 values were determined using isoproterenol.


RESULTS
In comparison with time O, neither anaphylaxis nor control samples had differences in receptor binding parameters with time. There were also no differences between anaphylaxis and control lung samples at any time point, and ratios of log control binding parameter/log anaphylaxis binding parameter ranged from 0.96 to 1.01.


CONCLUSIONS
Anaphylaxis of lung does not lead to acute changes in antagonist or agonist affinity for beta-receptors or changes in receptor concentration. Under the conditions studied, lung mast cell degranulation does not acutely alter the human lung beta-receptor system in ways that might account for the beta-adrenergic hyporesponsiveness found in allergic asthma.
Casale
T B
TB
Department of Internal Medicine, VA Medical Center, Iowa City, Iowa, USA.
D000328:Adult; D000707:Anaphylaxis / Q000378:metabolism*; D001667:Binding, Competitive; D015550:Cell Degranulation; D005260:Female; D006636:Histamine Release; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D010869:Pindolol / Q000378:metabolism; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D010869:Pindolol; D007545:Isoproterenol