CHARACTERIZATION OF THE RECEPTOR MEDIATING THE ANTI‐ANAPHYLACTIC EFFECTS OF β‐ADRENOCEPTOR AGONISTS IN HUMAN LUNG TISSUE <i>in vitro</i>

Butchers, P.R.; Skidmore, I.F.; Vardey, C.J.; Wheeldon, Alan

doi:10.1111/j.1476-5381.1980.tb10987.x

Cited by 85 publications

(46 citation statements)

References 16 publications

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“…In contrast to the results with PDE inhibitors and beclomethasone, salbutamol was effective in suppressing mast cell-derived histamine release. This is consistent with the findings of both Peters et al (1982) and Church & Hiroi (1987) who demonstrated that02 agonists could inhibit histamine release from human dispersed mast cells, an effect mediated by /2 receptors present on mast cells in human lung (Butchers et al, 1980). …”

Section: Discussionsupporting

confidence: 82%

The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti‐asthma drugs on inflammatory cell activation

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Moriggi

Ros

et al. 1996

British J Pharmacology

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1 This study aimed to evaluate the effects of phosphodiesterase (PDE) inhibitors and currently prescribed anti-asthma drugs for their ability to inhibit inflammatory cell activation in vitro. 2 Alveolar macrophages and eosinophils were isolated from the bronchoalveolar lavage (BAL) fluid of ovalbumin (Ovalb)-sensitized guinea-pigs. Opsonized zymosan (OZ) and PAF stimulated leukotriene B4 (LTB4) release from eosinophils was measured by radioimmunoassay. Ovalb-induced superoxide generation was measured by reduction of cytochrome C. 3 Monocytes were separated from human peripheral venous blood and mast cells were dispersed from human lung fragments. Lipopolysaccharide (LPS)-induced tumour necrosis factor-a (TNF-a) release from monocytes was measured by ELISA and anti-IgE stimulated histamine release from mast cells was measured by a radioenzymatic method. 4 The fl2 agonist, salbutamol inhibited TNF-a release from monocytes and histamine release from mast cells whilst having no effect on eosinophil-derived LTB4 release or macrophage superoxide generation. 5 The PDE 3 inhibitor, milrinone produced a concentration-related inhibition of TNF-a release from monocytes which achieved statistical significance at 10-5 M but inhibited LTB4 release from eosinophils and superoxide generation from macrophages only at the highest concentration (10-3 M) examined. Milrinone had no effect on histamine release from mast cells. 6 The selective PDE 4 inhibitors, denbufylline and rolipram and the corticosteroid, beclomethasone produced a concentration-related inhibition of LTB4 release from eosinophils, TNF-ax release from monocytes and superoxide generation from alveolar macrophages whilst having no effect on histamine release from mast cells. 7 The mixed PDE 3/4 inhibitor, benzafentrine produced a concentration-related inhibition of LTB4 release from eosinophils, TNF-a release from monocytes, superoxide generation from alveolar macrophages and histamine release from mast cells. 8 In conclusion these data clearly show that both established anti-asthma medication as well as PDE inhibitors have the potential to inhibit inflammatory cell activation in vitro but that the anti-secretory actions of fl2 agonists, corticosteroids and PDE inhibitors are distinct.

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Section: Discussionsupporting

confidence: 82%

The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti‐asthma drugs on inflammatory cell activation

Banner

Moriggi

Ros

et al. 1996

British J Pharmacology

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“…As early as 1936 (31) it was known that epinephrine could inhibit the release of histamine that occurred during the course of an anaphylactic reaction in guinea pig lung. Subsequent work showed a /-adrenergic receptor to be involved; however, attempts to define the P-receptor subgroup have been inconclusive (32). /3-Receptor agonists (epinephrine and/or isoproterenol) have also been found to enhance the activity of cytotoxic T cells (33), suppress antibody production (34,35), and affect lymphocyte proliferation following mitogen stimulation (36 ) and injected twice daily beginning at 1 dpi with prazosin (r, n = 6) or saline (e, n = 6).…”

Section: Discussionmentioning

confidence: 99%

Prazosin, an alpha 1-adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat.

Brosnan¹,

Goldmuntz²,

Cammer³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Prazosin, an antagonist of a1-adrenergic receptors, has been found to suppress the clinical and histological expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Suppression was more significant in females than in males and was a dose-dependent phenomenon. Analysis of the effect of other adrenergic receptor antagonists supports the conclusion that the suppressive effect of prazosin is a consequence of blockade of the a,-receptor since treatment with either the a2-antagonist yohimbine or the P-antagonist propranolol exacerbated the disease, whereas treatment with the long-acting mixed al/a2-antagonist phenoxybenzamine had some suppressive activity. Treatment with prazosin was also able to suppress clinical and histological signs of EAE in animals sensitized by adoptive transfer with activated spleen or lymph node cells. Whether prazosin acts through altering vascular permeability or the immune response, or both, remains to be determined.

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“…Histamine, leukotrienes and prostanoids released from tissue mast cells can cause bronchoconstriction, increase vascular permeability, stimulate the accumulation of inflammatory cells and contribute to hypersecretion of mucus (Lewis & Austen 1981;Wassermann, 1983). fl2-Adrenoceptor agonists such as salbutamol, as well as being potent bronchodilators, have been shown to inhibit the release of inflammatory and spasmogenic mediators from human lung tissue in vitro (Butchers et al, 1980), and to inhibit the rise in levels of circulating mediators after antigen challenge of asthmatic subjects in vivo (Howarth et al, 1985). These effects are believed to be mediated by fl2-adrenoceptors on lung mast cells (Butchers et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

“…fl2-Adrenoceptor agonists such as salbutamol, as well as being potent bronchodilators, have been shown to inhibit the release of inflammatory and spasmogenic mediators from human lung tissue in vitro (Butchers et al, 1980), and to inhibit the rise in levels of circulating mediators after antigen challenge of asthmatic subjects in vivo (Howarth et al, 1985). These effects are believed to be mediated by fl2-adrenoceptors on lung mast cells (Butchers et al, 1980). However, prior treatment of asthmatics with fi-adrenoceptor agonists, such as salbutamol, fails to attenuate the late asthmatic response after allergen challenge (Cockroft & Murdock, 1987).…”

Section: Introductionmentioning

confidence: 99%

Salmeterol: a potent and long‐acting inhibitor of inflammatory mediator release from human lung

Butchers¹,

Vardey²,

Johnson³

1991

British J Pharmacology

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154

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1 The effects of salmeterol, a novel long-actingf2-adrenoceptor agonist, have been investigated on antigen-induced mediator release from passively sensitized fragments of human lung in vitro.2 Salmeterol was a potent inhibitor of the release of histamine (-log IC5O = 8.54), leukotriene C4 (LTC4)/LTD4 (-log IC50 = 9.07) and prostaglandin D2 (-log IC50 = 8.81). It was slightly less potent (1-3 fold) than isoprenaline, but significantly more potent (10-35 fold) than salbutamol. 3 Propranolol competitively antagonized the inhibitory effects of salmeterol on histamine release (pA2 = 8.41) and LTCSLTD4 release, (pA2 = 8.40) indicating an action viaf,-adrenoceptors.4 The inhibitory effects of isoprenaline (20 nM) and salbutamol (200 nM) were removed after washing the lung tissue for 2 h and 4 h respectively. In contrast, the inhibitory effects of salmeterol (40 nM) were much longer-lasting, and were still evident after 20 h. 5 Salmeterol therefore exhibits potent and persistent inhibition of anaphylactic mediator release from human lung. This anti-inflammatory effect may be important for the therapeutic potential of salmeterol in the treatment of bronchial asthma.

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CHARACTERIZATION OF THE RECEPTOR MEDIATING THE ANTI‐ANAPHYLACTIC EFFECTS OF β‐ADRENOCEPTOR AGONISTS IN HUMAN LUNG TISSUE in vitro

Abstract: 1 The rank order of potency of six ,B-adrenoceptor agonists as inhibitors of the anaphylactic release of histamine from fragments of passively sensitized human lung in vitro was (--isoprenaline > (--adrenaline > (± -salbutamol > (-)

Cited by 85 publications

References 16 publications

The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti‐asthma drugs on inflammatory cell activation

The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti‐asthma drugs on inflammatory cell activation

Prazosin, an alpha 1-adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat.

Salmeterol: a potent and long‐acting inhibitor of inflammatory mediator release from human lung

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