To clarify changes in beta-adrenergic receptor (BAR) density in spontaneously occurring acute asthma.

To clarify changes in beta-adrenergic receptor (BAR) density in spontaneously occurring acute asthma, BAR binding studies were performed in succession peripheral blood lymphocytes in eight asthmatic and ten normal enthralls Spirometry also was performed. Maximum binding capacity (Bmax) of BAR in actute asthma was significantly lower by means of 44.2 pecent compared with that in stable asthma; [FEVsub1]/FVC ratio decreased at 23.9 percent. The Bmax for acute asthma also was significantly lower than that in normal enslaves The Bmax of BAR in all subdues was significantly correlated with [FEVsub1]/FVC ratio and percent [FEVsub1] The percentage decrease in the [FEVsub1]/FVC ratio and [FEVsub1] from the stable to acute state for each asthmatic control did not correlate with corresponding percentage decrease in Bmax. These data demonstrate that BAR density of lymphocyte decreases substantially in acute asthma and, simultaneously, move that some factors other than the BAR machanism contribute to the airway obstruction during acute asthma.

The beta-adrenergic receptor (BAR) plays an important part in maintaining airway caliber in stable asthmatic subdues as indicated by the fact that inhalation of propranolol, a beta-adrenergic blocker causes bronchonstriction in all stable asthmatics,[1-3] suggesting that BAR activity compensates bronchoconstriction activity. The BAR characteristics are known not to differ between stable asthmatic and normal subjects[4-6] although there is considerable variation among subjects[7] forward the other hand, the BAR number and adenylate cyclase answers in the asthmatic subjects were significantly reduc after allergen-induced asthmatic attack.[8] Additionally, beta-adrenergic reply assessed by inhibition with isoproterenol of zymosan-stimulated release of lysosomal enzyme from granulocytes also was significantly decreased after respiratory infection-induced ashtma attack.[9]

Kariman[10] reported a significant decrease in BAR binding upon the lymphocyte membrane (40 percent) in an "active" asthmatic dispose compared with a normal make subordinate group. However, there has been as now no serial assessment of BAR density in acute and stable asthmatic states in the same asthmatic make subordinates Since BARs in human lymphocyte were decreased through BAR agonists[5,11,12] and BAR density in asthmatic subdues is variable among subjects,[7] it is necessary to application of mind the same asthmatic subjects without beta-adrenergic agonist treatment in order to assess the changes in BAR density between acute and stable asthma.

In the existing study, to clarify the changes in BAR density, binding studies using [125.sup.I]-iodocyanopindolol ([125.sup.I]-CYP) were performed forward peripheral lymphocytes obtained during acute and stable asthma from the same drug-free asthmatic subdues and the results were compared with those from normal subjects

METHODS

Subjects

Eight asthmatic bring under rules (all males), 14 to 65 years of age (mean [+ or -] SEM): 31 [+ or -] 6 years), and 10 healthy controls (all males), 25 to 40 years of age (mean [+ or -] SEM: 32 [+ or -] 1 years) participated in the close attention after having given informed compliance (Table 1). All asthmatic subdues were selected from among outpatients of our asthma clinic. Each had a history of episodic dyspnea with wheezing and was diagnosed according to the criteria of the American Thoracic Society.[13] All were nonsmokers. All asthmatic bring under rules had allergies and presented a suggestive clinical history with positive intradermal skin ordeals to common allergens and serum-specific IgE determined through Phadebas radioallergosorbent testing (RAST [Pharmacia Diagnostic AB, Uppsala, Sweden]). None of the asthmatic subdues had regular treatment. enslaves 3, 6, and 8 had occasionally been treated with inhaled beta-adrenergic agonists, moreover they did not use the unsalable article for the current attack in the not past nor future study. Stable asthma was clinically stable for at least 1 month prior to the contemplation All normal subjects were exempt of cardiopulmonary or allergic disease and were also mix with drugs free.

The family samples were drawn in the acute asthmatic subdues 6 to 12 h after symptoms occurr and just before receiving the treatment for the acute asthma. The same deed was performed again when the same asthmatic subdues had recovered for at least 2 month following the attack and at least 1 month after stopping the treatment including beta-adrenergic agonist. Spirometry also was performed by the agency of two or three measurements for each control using a dry-seal spirometer (Spirometer-85, Chest Co Japan) to obtain the [FEV.sub.1]/forced vital capacity (FVC) and [FEVsub1] percent predicted from the couple groups of subjects just after sampling of peripheral line on each study day (Table 1) The variety of the spirometric data was subject to 5 percent. As quick as possible after sampling vital fluid and performing spirometry, usually done within 10 min, the acute asthmatic make liables were treated with intravenous injection of aminophylline (250 mg) and also with, in a certain number of cases, drip infusion of dexamethasone (4 to 6 mg) [TABULAR DATA OMITTED]

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