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Inhibition of extracellular nucleotides hydrolysis intensifies the allergic bronchospasm. A novel protective role of ectonucleotidases
Author(s) -
Chávez J.,
Vargas M. H.,
RebollarAyala D. C.,
DíazHernández V.,
CruzValderrama J. E.,
FloresSoto E.,
FloresGarcía M.,
JiménezVargas N. N.,
BarajasLópez C.,
Montaño L. M.
Publication year - 2013
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12113
Subject(s) - purinergic receptor , p2y receptor , suramin , ppads , receptor , bronchospasm , apyrase , chemistry , p2 receptor , bronchoalveolar lavage , extracellular , immunology , pharmacology , endocrinology , medicine , biochemistry , lung , asthma
Background Nucleotides released to the extracellular space stimulate purinergic receptors, and their effects are modulated by ectonucleotidases. The role of ATP in the allergic bronchospasm has been scantly studied. Methods We used several techniques (plethysmography, organ baths, confocal microscopy, RT ‐ PCR , ATP measurement) to explore the role of nucleotides and ectonucleotidases in the allergic bronchospasm in guinea pigs. Results While allergenic challenge with a low‐dose ovalbumin (OVA) only produced a small bronchospasm (~2‐fold the basal lung resistance), previous inhibition of ectonucleotidases by ARL‐67156 greatly intensified this response (~11‐fold the basal lung resistance, with 44% mortality). Bronchoalveolar lavage fluid obtained during this bronchospasm contained increased ATP concentration. This potentiation was abolished by antagonism of purinergic receptors (suramin+RB2) or TXA 2 receptor (SQ29548), or by intratracheal apyrase. In tracheal rings and lung parenchyma strips, OVA caused a concentration‐dependent contraction. Suramin+RB2 or levamisole produced a significant rightward displacement of this response, and ARL‐67156 did not modify it. Platelets stimulated with OVA released ATP. Confocal images of nonsensitized tracheas showed slight fluorescence for P2Y 6 receptors in epithelium and none for P2Y 4 . Sensitized animals showed strong fluorescence to both receptors and to alkaline phosphatase in the airway epithelium. This correlated with a large increment in mRNA for P2Y 4 and P2Y 6 receptors in sensitized animals. Conclusions Nucleotides greatly potentiate the allergic bronchospasm when ectonucleotidases activity is diminished, and this effect is probably favored by the upregulation of P2Y 4 and P2Y 6 receptors in airway epithelium during sensitization. These results prompt for further research on these mechanisms in human asthma.