Inhibition of extracellular nucleotides hydrolysis intensifies the allergic bronchospasm. A novel protective role of ectonucleotidases

• DOI: 10.1111/all.12113
• Publication Date: 2013-02-19T11:20:03Z
• Authors: J. Chávez; M. H. Vargas; D. C. Rebollar‐Ayala; V. Díaz‐Hernández; J. E. Cruz‐Valder...; E. Flores‐Soto; M. Flores‐García; N. N. Jiménez‐Vargas; C. Barajas‐López; L. M. Montaño
• Keywords: P2Y receptor; PPADS; Apyrase; P2 receptor

Abstract Background Nucleotides released to the extracellular space stimulate purinergic receptors, and their effects are modulated by ectonucleotidases. The role of ATP in allergic bronchospasm has been scantly studied. Methods We used several techniques (plethysmography, organ baths, confocal microscopy, RT ‐ PCR , measurement) explore nucleotides ectonucleotidases guinea pigs. Results While allergenic challenge with a low‐dose ovalbumin (OVA) only produced small (~2‐fold basal lung resistance), previous inhibition ARL‐67156 greatly intensified this response (~11‐fold resistance, 44% mortality). Bronchoalveolar lavage fluid obtained during contained increased concentration. This potentiation was abolished antagonism receptors (suramin+RB2) or TXA 2 receptor (SQ29548), intratracheal apyrase. In tracheal rings parenchyma strips, OVA caused concentration‐dependent contraction. Suramin+RB2 levamisole significant rightward displacement response, did not modify it. Platelets stimulated ATP. Confocal images nonsensitized tracheas showed slight fluorescence for P2Y 6 epithelium none 4 . Sensitized animals strong both alkaline phosphatase airway epithelium. correlated large increment mRNA sensitized animals. Conclusions potentiate when activity is diminished, effect probably favored upregulation sensitization. These results prompt further research on these mechanisms human asthma.