Acute effects of in vitro mast cell degranulation on human lung muscarinic receptors.
Allergic asthmatic patients have baseline airway cholinergic hyperresponsiveness that rapidly increases after antigen inhalation and mediator release. We therefore examined whether anaphylaxis of human lung tissue (exposure to mast cell mediators) acutely modulated the human lung muscarinic receptor system in ways that might account for these increased in vivo cholinergic airway responses. Fresh thoracotomy peripheral lung samples from 24 patients were incubated with (anaphylaxis) or without (control) anti-IgE (1:100) for up to 90 min. The average percentage of histamine released ranged from 20 to 30% in anaphylaxis and 3 to 5% in control samples, with > 80% of total histamine released by 15 to 30 min. Lung fragments were quick frozen at various times after anti-IgE for analyses of muscarinic receptor binding parameters. Antagonist Kd (dissociation constant) and receptor concentration values were determined using [3H]quinuclidinyl benzilate, and agonist IC50 values were determined using carbachol. In comparison with time 0, 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 1.04. Thus, anaphylaxis of lung does not lead to acute changes in antagonist or agonist affinity for muscarinic receptors or changes in receptor concentration. Therefore, under the conditions studied, lung mast cell degranulation does not appear to acutely alter the human lung muscarinic receptor system in ways that might account for the increased in vivo lung cholinergic hyperresponsiveness found in allergic asthmatic patients.
Casale
T B
TB
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa.
D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000378:metabolism; D002217:Carbachol / Q000378:metabolism; D015550:Cell Degranulation; D005260:Female; D006636:Histamine Release; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008875:Middle Aged; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism*
D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol