90 Characterization of the human peripheral lung adenosine receptor

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CHARACPERIZATION OF THE HUMANPERIPHERAL m ADENCSINE RECEPTOR. JP Joad, MD, Chicago, IL. Since adenosine causes airway obstruction in asthmatic persons and is produced in the lung under conditions of hypoxia and mast cell degranulation, abnormal adenosine responsiveness may play a role in asthma. This study characterized the human lung adenosine recep tor using radioligand techniques. Optiml incubation conditions were determined which provided the greatest specific binding of the adenosine receptor agonist, ethylcarboxamidoadenosine, 5'-N-[adenine-2,8-3H1, (t3Hl-WX) Bound and to human lung plasma membranes. free ligand were separated using rapid vacuum filtration. The optimal incubation conditions included: 4 C, pH 7.4, 5mM MgC12, 1.8mc~ pro30 minutes incubation time. Using tein/ml, these conditions, multiple radioligand experiments were then performed in which 1OnM [3HlNKCA was incubated in the presence of various concentrations of unlabeled NECA, and the data were analyzed using the curve fitting program LIGAND. The data fit a single binding site with a Kd of 152 +3OnM (mean+SEM), and a receptor concentratTon of 473+F5fm/nq protein. Agonists and antagonists c&peted with [3H]NSCA in the following rank order of potency (Kd~SEM in uM): NECA (0.152 +0.030), isobuR-N6tyl-1-methylxanthine (22.0+6.8), (phenylisopropyl) adensoine Tl29+68), theophylline (215+_80). Thus, human perTphera1 lung contains a large number of moderate affinity receptor adenosine receptors of the A2 subtype.

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PASSIVE TRANSFER OF BRONCHIAL REACTIVITY TO TC -HSA) As A MODtL CRITERION FOR Igt Mm ASTHMA CAUStD M.D., R w RtACl'T?mCALS . MS Dykewicz, Patterson, M.D., KE Harris, B.S., Chlcago, Illinois Serum from a worker with trimellitic anhydride (TMA) asthma that contained high titers of IgE to TM-HSA was aerosolized into the lungs of rhesus monkeys. When monkeys were challenged with aerosolized TM-HSA 48 hours later, pulmonary functions demonstrated acute airway responses similar to those of IgE mediated bronchospasm in ascaris sensitive monkeys. The monkeys studied had no airway reactivity when challenged with TM-HSA one week after the first positive TM-HSA response. Heat-treated donor serum did not confer passive bronchial reactivity to TM-HSA indicating that the serum factor responsible for passive sensitization was IgE antibody. These results and previous studies fulfill for TMA asthma all four criteria that we now postulate should be present in asthma caused by any reactive chemical that mediates bronchospasm by IgE to chemical haptenprotein conjugates. 1) Humans with disease have defined acute airway responses after challenge with the reactive chemical at levels that do not elicit responses in normals. 2) The chemical reacts with self proteins to form conjugates demonstrable by physical-chemical means. 3) Serum anti-conjugate IgE can be demonstrated by in vitro or in vitro tests. 4) Cutaneous and -.~r~eactivity can be passively transferred with serum containing anti-conjugate IgE.

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RELATIVE RESPONSIVENESS TO LEUKOTRIENE E4, METHACHOLINE AND HISTAMINE IN NORMAL AND ASTHMATIC SUBJECTS. S P O'Hickey. J P Arm, B W Spur, P J Rees. T H Lee. London U.K. The relative bronchoconstrictine ootencies of methacholine and histami:e' have been LTE4, compared in asthmatic and normal subjects. LTE4 responsiveness in asthmatic subjects, as measured by the dose which produced a 35% fall in airways specific conductance (PD35), ranged from 1.2 to 24.4 nmol (Geom mean, 6.8 nmol, n=16). This was significantly less than the PD35 in normal subjects (range 3.2 to 370 nmol, geom mean 64.5 nlnol, n=7, p
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GASTRO-OESOPHAGEAL REFLUX (GOR) AND CHILDHOOD A P M Gustafsson, M.D., L Tibbling M.D., N-I M &ellman,M.D., Linkiiping, Sweden This study aimed at revealing 1) the frequency of oesophageal dysfunction (OD) and GOR in asthmatic children and adolescents; and 2) the importance of acid reflux for asthma symptoms and lung function. Fifty-five subjects, 7-19 years of age, with moderate or severe asthma and 30 controls, 9-18 years of age, were investigated with oesophageal manometry combined with pH reflux tests, an acid perfusion test and an acid clearing test.Sixty % of the asthmatic subjects vs. 14% of the controls had OD (p40 kg b.w.) or placebo, in the evenings. Asthma symptoms and twice daily Peak Expiratory Flow Rates were recorded in daily record cards. FEVl and bronchial histamine thresholds were similar after placebo and ranitidine periods. Neither the asthmatics with 00 and pathological GOR nor those without these findings improved during ranitidine treatment. We conclude that GOR and OD are commonly found in children ad adolescents with asthma. The importance of acid reflux as a trigger of asthma is however questionable in most subjects with these findings.

and

methacholine

responsiveness.

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