Therapeutic Applications

Overview

Journal Subcell Biochem

Publisher Springer

Specialty Biochemistry

Date 2011 May 12

PMID 21560050

Authors

Stephen Tilley

Jon Volmer

Maryse Picher

Affiliations

Soon will be listed here.

Abstract

The current treatments offered to patients with chronic respiratory diseases are being re-evaluated based on the loss of potency during long-term treatments or because they only provide significant clinical benefits to a subset of the patient population. For instance, glucocorticoids are considered the most effective anti-inflammatory therapies for chronic inflammatory and immune diseases, such as asthma. But they are relatively ineffective in asthmatic smokers, and patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). As such, the pharmaceutical industry is exploring new therapeutic approaches to address all major respiratory diseases. The previous chapters demonstrated the widespread influence of purinergic signaling on all pulmonary functions and defense mechanisms. In Chap. 8, we described animal studies which highlighted the critical role of aberrant purinergic activities in the development and maintenance of chronic airway diseases. This last chapter covers all clinical and pharmaceutical applications currently developed based on purinergic receptor agonists and antagonists. We use the information acquired in the previous chapters on purinergic signaling and lung functions to scrutinize the preclinical and clinical data, and to realign the efforts of the pharmaceutical industry.

References

Hua X, Erikson C, Chason K, Rosebrock C, Deshpande D, Penn R . Involvement of A1 adenosine receptors and neural pathways in adenosine-induced bronchoconstriction in mice. Am J Physiol Lung Cell Mol Physiol. 2007; 293(1):L25-32. DOI: 10.1152/ajplung.00058.2007. View

Ethier M, Madison J . Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells. Am J Respir Cell Mol Biol. 2006; 35(4):496-502. PMC: 2065849. DOI: 10.1165/rcmb.2005-0290OC. View

Banerjee S, Young H, Volmer J, Blackburn M . Gene expression profiling in inflammatory airway disease associated with elevated adenosine. Am J Physiol Lung Cell Mol Physiol. 2002; 282(2):L169-82. DOI: 10.1152/ajplung.00243.2001. View

Chhabra P, Wang K, Zeng Q, Jecmenica M, Langman L, Linden J . Adenosine A(2A) agonist administration improves islet transplant outcome: Evidence for the role of innate immunity in islet graft rejection. Cell Transplant. 2010; 19(5):597-612. DOI: 10.3727/096368910X491806. View

Godfrey S, Springer C, Noviski N, Maayan C, Avital A . Exercise but not methacholine differentiates asthma from chronic lung disease in children. Thorax. 1991; 46(7):488-92. PMC: 463237. DOI: 10.1136/thx.46.7.488. View

Vidal B, Nueda A, Esteve C, Domenech T, Benito S, Reinoso R . Discovery and characterization of 4'-(2-furyl)-N-pyridin-3-yl-4,5'-bipyrimidin-2'-amine (LAS38096), a potent, selective, and efficacious A2B adenosine receptor antagonist. J Med Chem. 2007; 50(11):2732-6. DOI: 10.1021/jm061333v. View

Riteau N, Gasse P, Fauconnier L, Gombault A, Couegnat M, Fick L . Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med. 2010; 182(6):774-83. DOI: 10.1164/rccm.201003-0359OC. View

Drakatos P, Lykouras D, Sampsonas F, Karkoulias K, Spiropoulos K . Targeting leukotrienes for the treatment of COPD?. Inflamm Allergy Drug Targets. 2009; 8(4):297-306. DOI: 10.2174/187152809789352177. View

Ball H, Sandrasagra A, Tang L, Van Scott M, Wild J, Nyce J . Clinical potential of respirable antisense oligonucleotides (RASONs) in asthma. Am J Pharmacogenomics. 2003; 3(2):97-106. DOI: 10.2165/00129785-200303020-00003. View

10.

Gessi S, Varani K, Merighi S, Cattabriga E, Pancaldi C, Szabadkai Y . Expression, pharmacological profile, and functional coupling of A2B receptors in a recombinant system and in peripheral blood cells using a novel selective antagonist radioligand, [3H]MRE 2029-F20. Mol Pharmacol. 2005; 67(6):2137-47. DOI: 10.1124/mol.104.009225. View

11.

Chipps B . Inhaled corticosteroid therapy for patients with persistent asthma: learnings from studies of inhaled budesonide. Allergy Asthma Proc. 2009; 30(3):217-28. DOI: 10.2500/aap.2009.30.3201. View

12.

Matot I, Einav S, Weiniger C, Pearl R, Abramovitch R, Joshi B . Lung injury after in vivo reperfusion: outcome at 27 hours after reperfusion. Anesthesiology. 2008; 109(2):269-78. PMC: 2688693. DOI: 10.1097/ALN.0b013e31817f5b90. View

13.

Nyce J . Insight into adenosine receptor function using antisense and gene-knockout approaches. Trends Pharmacol Sci. 1999; 20(2):79-83. DOI: 10.1016/s0165-6147(99)01305-x. View

14.

BROWN R, Clarke G, Ledbetter C, Hurle M, Denyer J, Simcock D . Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects. Eur Respir J. 2007; 31(2):311-9. DOI: 10.1183/09031936.00003707. View

15.

Sullivan G, Lee D, Ross W, DiVietro J, Lappas C, Lawrence M . Activation of A2A adenosine receptors inhibits expression of alpha 4/beta 1 integrin (very late antigen-4) on stimulated human neutrophils. J Leukoc Biol. 2003; 75(1):127-34. DOI: 10.1189/jlb.0603300. View

16.

Gessi S, Merighi S, Varani K, Leung E, Mac Lennan S, Borea P . The A3 adenosine receptor: an enigmatic player in cell biology. Pharmacol Ther. 2007; 117(1):123-40. DOI: 10.1016/j.pharmthera.2007.09.002. View

17.

Lisle T, Gazoni L, Fernandez L, Sharma A, Bellizzi A, Shifflett G . Inflammatory lung injury after cardiopulmonary bypass is attenuated by adenosine A(2A) receptor activation. J Thorac Cardiovasc Surg. 2008; 136(5):1280-7. PMC: 2652167. DOI: 10.1016/j.jtcvs.2008.07.010. View

18.

Lee J, Jhun B, Oh Y, Lee J, Choe W, Baik H . Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neurosci Lett. 2005; 396(1):1-6. DOI: 10.1016/j.neulet.2005.11.004. View

19.

Saha S, Berry M, Parker D, Siddiqui S, Morgan A, May R . Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol. 2008; 121(3):685-91. PMC: 3992379. DOI: 10.1016/j.jaci.2008.01.005. View

20.

Ford P, Durham A, Russell R, Gordon F, Adcock I, Barnes P . Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD. Chest. 2010; 137(6):1338-44. DOI: 10.1378/chest.09-2363. View