Increased pulmonary α-adrenergic and reduced β-adrenergic receptors in experimental asthma

Barnes, Peter J.; Dollery, C. T.; MacDermot, John

doi:10.1038/285569a0

Cited by 173 publications

(58 citation statements)

References 14 publications

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“…Furthermore indomethacin has been shown to inhibit the relaxant effects of prostaglandins (Yamaguchi et al, 1976;Burka & Paterson, 1980). Many drugs including prostacyclin (MacDermot & Barnes, 1980) and VIP (Robberecht et al, 1981) have been shown to activate adenylate cyclase of lung tissue. We have extended these findings to include forskolin.…”

Section: Discussionmentioning

confidence: 99%

Bronchodilator‐mediated relaxation of normal and ovalbumin‐sensitized guinea‐pig airways: lack of correlation with lung adenylate cyclase activation

Burka

Saad

1984

British J Pharmacology

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1 Isoprenaline, vasoactive intestinal peptide (VIP), prostaglandin E2 (PGE2) and forskolin caused a dose-dependent relaxation of normal and ovalbumin-sensitized guinea-pig tracheal spirals and lung parenchymal strips in vitro. There was no difference in magnitude of relaxation or sensitivity to these relaxants between normal and sensitized tissues. The rank order of potency (concentration of each drug at which 50% of the maximum is obtained) for these relaxants on both trachea and parenchyma was VIP > isoprenaline > PGE2 > forskolin, although the parenchyma was more sensitive than the trachea.2 The rank order of efficacy of the drugs used in relaxing both the trachea and lung parenchyma was isoprenaline (10 1M) > forskolin (30 pM) > VIP (0.1 pM) > PGE2 (10 AM). PGE2 at concentrations greater than 1 JAM sometimes contracted the lung strip.3 Pretreatment with indomethacin (8.5 pM), a cyclo-oxygenase inhibitor, reduced the resting tone of tracheal spirals, but did not significantly affect the tone of lung strips. Indomethacin-pretreatment did not affect drug-induced relaxations of either normal or sensitized tracheal spirals. However, both normal and sensitized indomethacin-pretreated lung strips relaxed significantly less (P <0.05) to isoprenaline, PGE2 and forskolin. Indomethacin-pretreatment did not affect sensitivity of normal and sensitized trachea or parenchyma to the relaxant drugs. 4 All the relaxant drugs used stimulated adenylate cyclase activity in normal or sensitized lung parenchyma membrane preparations. The rank order of efficacy (maximal activation) was forskolin> isoprenaline = VIP > PGE2. There was no difference in response between normal and sensitized lungs. Adenylate cyclase activity of normal lung was stimulated as follows: forskolin (1001M), 500.0 ± 50.0%; isoprenaline (100 tM), 186.0 ± 29.0%; VIP (10 M), 213.0 ± 19.0% and PGE2 (100 1M), 155.0 ± 23.0% of basal activity. Similar values were obtained for sensitized lung parenchyma.5 Indomethacin--pretreatment did not significantly affect normal or sensitized lung adenylate cyclase stimulation by isoprenaline, VIP, forskolin or PGE2. 6 It was concluded that: (a) Immunological sensitization to ovalbumin does not induce hypoactivity of relaxant drug receptors and/or the adenylate cyclase system of the airway tissues of the guinea-pig. (b) There is an apparent lack of correlation between tissue relaxation in vitro and adenylate cyclase activity since the rank order of the efficacy of a range of relaxants was different for the two effects and furthermore indomethacin-treatment of airway tissues yielded differential results.

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Section: Discussionmentioning

confidence: 99%

Bronchodilator‐mediated relaxation of normal and ovalbumin‐sensitized guinea‐pig airways: lack of correlation with lung adenylate cyclase activation

Burka

Saad

1984

British J Pharmacology

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“…The (Kneussl & Richardson, 1971) and peripheral (Black et al, 1981). There is, in addition, evidence for a change in a-receptor number in pulmonary disease states on the basis of animal studies (Barnes et al, 1980). The results of in vivo studies however, have been conflicting.…”

mentioning

confidence: 93%

Comparison between airways response to an alpha‐adrenoceptor agonist and histamine in asthmatic and non‐asthmatic subjects.

Jl¹,

Salome²,

Yan³

et al. 1982

Brit J Clinical Pharma

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“…Although beta-adrenergic agonists are the most potent and widely-used bronchodilator agents, an allergic reaction and/or administration of a high dose of a betaadrenergic agonist reduces their relaxant effects due to a decreased number of beta-adrenergic receptors [18][19][20][21], and a dysfunction of signalling at postreceptor sites in bronchial asthma [22,23]. Whilst the relaxant effects of beta-adrenergic agonists on the basal and developed tone of airway smooth muscle have been extensively investigated, it is not known whether an allergic reaction would reduce the spasmolytic effect of the KATP openers, and whether the administration of a high dose of a beta-adrenergic agonist would modulate the action of the KATP openers.…”

Section: Allergic Responses Reduce the Relaxant Effect Of β-Agonists mentioning

confidence: 99%

Allergic responses reduce the relaxant effect of beta-agonists but not potassium channel openers in guinea-pig isolated trachea

Houjou¹,

Iizuka²,

Dobashi³

et al. 1996

Eur Respir J

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This study was conducted to determine whether the relaxant effect of adenosine triphosphate (ATP)-sensitive potassium channel (KATP) openers on airway smooth muscle are reduced during the hyporesponsiveness of beta-adrenergic receptors. Isometric tension was measured and dose-response curves were constructed for levcromakalim (a KATP opener), Y-26763 (another KATP opener), isoprenaline and theophylline in guinea-pig isolated trachea that was challenged with ovalbumin or pretreated in vitro with either isoprenaline or the KATP openers. Antigen challenge in vitro significantly reduced the potency but not the efficacy of isoprenaline in tracheal strips from actively sensitized guinea-pigs. The concentration of drug that produced a half-maximum inhibition (IC50) was 0.014 +/- 0.004 microM in the challenge group versus 0.006 +/- 0.001 microM in the control group (p < 0.05; n = 9). The IC50 of levcromakalim (1.73 +/- 0.17 microM; n = 6) and of theophylline (110 +/- 3.1 microM; n = 6) were unaffected. Exposure to 4 microM isoprenaline for 30 min evoked beta-adrenergic hyporesponsiveness: the IC50 of isoprenaline rose significantly from 0.010 +/- 0.001 to 0.017 +/- 0.002 microM (p < 0.01; n = 6). No effect was observed on the relaxant actions of levcromakalim and theophylline. In contrast, prior incubation with either levcromakalim or Y-26763 (300 microM for 30 min) significantly reduced the subsequent potency and efficacy of levcromakalim, but did not alter the effects of isoprenaline and theophylline. We conclude that the relaxant effect of the adenosine triphosphate-sensitive potassium channel openers was independent of beta-adrenergic hyporesponsiveness in airway smooth muscle of guinea-pigs.

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Increased pulmonary α-adrenergic and reduced β-adrenergic receptors in experimental asthma

Cited by 173 publications

References 14 publications

Bronchodilator‐mediated relaxation of normal and ovalbumin‐sensitized guinea‐pig airways: lack of correlation with lung adenylate cyclase activation

Bronchodilator‐mediated relaxation of normal and ovalbumin‐sensitized guinea‐pig airways: lack of correlation with lung adenylate cyclase activation

Comparison between airways response to an alpha‐adrenoceptor agonist and histamine in asthmatic and non‐asthmatic subjects.

Allergic responses reduce the relaxant effect of beta-agonists but not potassium channel openers in guinea-pig isolated trachea

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