Alpha- and beta-adrenergic-receptor systems in bronchial asthma and in subjects without asthma: reduced mononuclear cell beta-receptors in bronchial asthma.
We assessed the adrenergic-receptor system in individuals with bronchial hyperreactivity, beta-Adrenergic receptors on mononuclear cell membranes, alpha-adrenergic receptors on platelet membranes, and the cAMP response in these cell types to different stimuli, including platelet-activating factor (PAF), were determined. Studies were assessed in 10 subjects with mild asthma, six methacholine-sensitive subjects without asthma, and 10 normal subjects. The density and affinity of beta-receptors and alpha-receptors were determined by Scatchard analysis. Our findings were that (1) subjects with asthma had a significantly lower density of beta-receptors compared to normal subjects, (2) subjects with asthma had a significantly lower cAMP response to isoproterenol stimulation compared to the two other groups, (3) in subjects without asthma. PAF decreased the basal cAMP level and significantly inhibited the response to isoproterenol stimulation, (4) there was no difference in density and affinity of platelet alpha-receptors or in platelet cAMP responses to stimulation by alpha-agonists among these three groups, and (5) neither cAMP response or beta-receptor density on mononuclear cells were significantly correlated with pulmonary-function tests (FEV/FVC times 100), sensitivity to methacholine, or cold-air inhalation. These results suggest that patients with asthma may have a lower isoproterenol cAMP response and decreased density of beta-adrenergic receptors on mononuclear cells in the absence of beta-agonist therapy. It is speculated that release of PAF and other mediators secondary to allergen exposure, even in the absence of overt attacks of asthma, may inhibit the response to endogenous or exogenous beta-adrenergic agonists.
Sato
T
T
Department of Medicine, Creighton University School of Medicine, Omaha, NE 68178.
Bewtra
A K
AK
Hopp
R J
RJ
Nair
N
N
Townley
R G
RG
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism; D001985:Bronchial Provocation Tests; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D009000:Monocytes / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values; D012129:Respiratory Function Tests
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D016210:Methacholine Chloride