Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease

Abstract

Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease. R. Polosa. #ERS Journals Ltd 2002. ABSTRACT: Adenosine administration by inhalation elicits concentration-related bronchoconstriction in subjects with asthma and chronic obstructive pulmonary disease (COPD). The mechanisms of adenosine-induced bronchoconstriction appear to involve a selective interaction with activated mast cells with subsequent release of preformed and newly-formed mediators. Further evidence linking adenosine signalling to asthma and COPD comes from the finding that many cell types that play important roles in the exacerbation of these conditions express adenosine receptors and demonstrate relevant effects through stimulation of these receptors.Therefore, blockade of these receptors may be a valuable approach to the treatment of asthma and chronic obstructive pulmonary disease. Promising adenosine-receptor targets for novel therapeutics of asthma and chronic obstructive pulmonary disease have recently been identified in a number of inflammatory cell types, including mast cells, eosinophils, lymphocytes, neutrophils, and macrophages. The recent characterisation of the A 2B receptors indicates the human lung mast cell as one of the most strategic cellular targets. Eur Respir J 2002; 20: 488-496.

Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors

“…Some studies have identified the expression of both adenosine A 2A and A 2B receptors in mast cells [37]. It has been proposed that the inosine precursor, adenosine, acting through these receptors, can respectively suppress or stimulate mast cells activation being the latter related with bronchoconstrictor effects [37]. In contrast, it is described that inosine has no effect on airway calibre, and it is suggested that bronchoconstriction is a response specific to adenosine [38].…”

“…Some studies have identified the expression of both adenosine A 2A and A 2B receptors in mast cells [37]. It has been proposed that the inosine precursor, adenosine, acting through these receptors, can respectively suppress or stimulate mast cells activation being the latter related with bronchoconstrictor effects [37].…”

Pharmacotherapy of Asthma

“…Novel bronchodilator compounds such as vasoactive intestinal peptide (VIP), atrial natriuretic peptide (ANP), and prostaglandin E analogs are undergoing investigation. 28 Despites some promising success, the main draw of using peptides as therapeutic agents, their instability, still needs to be overcome.…”

Changes in Adenosine Metabolism in Asthma. A Study on Adenosine, 5&#39-NT, Adenosine Deaminase and Its Isoenzyme Levels in Serum, Lymphocytes and Erythrocytes

“…However, under conditions of high-energy demand, AMP cannot be reconverted and it is metabolised to adenosine by 5ʹ-nucleotidase (plasma membrane bound mainly as well as cytoplasmic) [31]. Intracellular levels of adenosine are kept low by its conversion to AMP by the enzyme adenosine kinase and to inosine by adenosine deaminase, but when energy demands are greater as in inflammation, deamination predominates [32]. Extracellular adenosine diffuses back into the cell through the operation of an energy-independent nucleoside transporter [33].…”