Mechanisms and significance of adenosine‐induced bronchoconstriction in asthma

Holgate, Stephen T.; Mann, J. S.; Church, Martin K.; Cushley, M. J.

doi:10.1111/j.1398-9995.1987.tb00369.x

Cited by 15 publications

(15 citation statements)

References 17 publications

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“…Similar concentration-effect curves were generated for UTP and ATP in K562 cells, a cell line that also lacks endogenous P2U receptors (11), transiently transfected with HP2U (data not shown). Clearly, the agonist specificities most closely fit the pharmacological classification of the P2u receptor (18).…”

Section: And Discussionmentioning

confidence: 60%

Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy.

Parr

Sullivan

Paradiso

et al. 1994

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

382

258

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The Cl- secretory pathway that is defective in cystic fibrosis (CF) can be bypassed by an alternative pathway for Cl- transport that is activated by extracellular nucleotides. Accordingly, the P2 receptor that mediates this effect is a therapeutic target for improving Cl- secretion in CF patients. In this paper, we report the sequence and functional expression of a cDNA cloned from human airway epithelial (CF/T43) cells that encodes a protein with properties of a P2U nucleotide receptor. With a retrovirus system, the human airway clone was stably expressed in 1321N1 astrocytoma cells, a human cell line unresponsive to extracellular nucleotides. Studies of inositol phosphate accumulation and intracellular Ca2+ mobilization induced by extracellular nucleotides in 1321N1 cells expressing the receptor identified this clone as the target receptor in human airway epithelia. In addition, we independently isolated an identical cDNA from human colonic epithelial (HT-29) cells, indicating that this is the same P2U receptor that has been functionally identified in other human tissues. Expression of the human P2U receptor (HP2U) in 1321N1 cells revealed evidence for autocrine ATP release and stimulation of transduced receptors. Thus, HP2U expression in the 1321N1 cell line will be useful for studying autocrine regulatory mechanisms and in screening of potential therapeutic drugs.

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Section: And Discussionmentioning

confidence: 60%

Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy.

Parr

Sullivan

Paradiso

et al. 1994

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

382

258

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“…28 Previous studies have focused on the pathways mediating exogenous adenosine-induced bronchoconstriction. 29,30 However, it remains unclear whether endogenous adenosine produces direct bronchoconstriction in patients with asthma. Adenosine inhalation-induced bronchoconstriction in patients with asthma can be largely (80%) relieved by pretreatment with either mast cell membrane stabilizers or antihistamines.…”

Section: The Potency Of Adenosine To Elicit Lung Mast Cell Degranulationmentioning

confidence: 99%

Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells

Hua

Chason

Fredholm

et al. 2008

Journal of Allergy and Clinical Immunology

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“…The involvement of adenosine in asthma has been the subject of considerable attention over the years, after it was shown that it produced powerful bronchoconstriction in asthma, although it had little effect in healthy lungs; xanthines, antagonists of adenosine receptors, were widely used for treatment of asthma (for reviews, see Persson, 1982;Kawasaki et al, 1983;Holgate et al, 1987Holgate et al, , 1990Feoktistov and Biaggioni, 1996;Fozard and Hannon, 2000;Meade et al, 2001;Fozard and McCarthy, 2002;Holgate, 2002Holgate, , 2005Polosa et al, 2002;Fozard, 2003;Lee et al, 2003;Livingston et al, 2004;Caruso et al, 2006Caruso et al, , 2009Russo et al, 2006;Brown et al, 2008b;Wilson, 2008). It was suggested that the hyper-responsive effects of adenosine in isolated bronchi was due to indirect actions by liberation of histamine and leukotrienes (Björck et al, 1992).…”

Section: A Asthmamentioning

confidence: 99%