Dictionary of Allergies .. Adenylcyclase

Adenylcyclase

A cell membrane localized enzyme, which converts ATP to cyclic 3'5' adenosine monophosphate (cAMP), the second messenger which induces the beta adrenergic responses. The effects of β2 adrenergic agents appear to be mediated by stimulation of adenylate cyclase, with a consequent rise of intracellular cyclic adenosine monophosphate (c AMP). This increase of cAMP antagonizes the action of vasoactive substances derived from mast cells inhibiting after that, the bronchial smooth muscle spasm in asthma. (see receptors).

The accumulation of evidence implicating a role for adenosine in the pathogenesis of asthma has led to investigations into all adenosine receptor subtypes as potential therapeutic targets for the treatment of asthma. Selective A(1) receptor antagonists are currently in preclinical development since adenosine has been shown experimentally to mediate various features of asthma through this receptor such as bronchoconstriction, mucus secretion and inflammation. The A(2A) receptor is expressed on most inflammatory cells implicated in asthma, and as A(2A) stimulation activates adenylate cyclase and consequently elevates cAMP, selective A(2A) receptor agonists have now reached clinical development. However, initial reports concerning their efficacy are inconclusive. A(2B) receptor antagonists are also under investigation based on the rationale that inhibiting the effects of adenosine on mast cells would be beneficial, in addition to other reported pro-inflammatory effects mediated by the A(2B) receptor on cells such as airway smooth muscle, epithelial cells and fibroblasts. Whilst the effects in pre-clinical models are promising, their efficacy in the clinical setting has also yet to be reported. Finally, adenosine A(3) receptor stimulation has been demonstrated to mediate inhibitory effects on eosinophils since it also elevates cAMP. However, some experimental reports suggest that A(3) antagonists mediate anti-inflammatory effects, thus the rationale for A(3) receptor ligands as therapeutic agents remains to be determined. In conclusion, establishing the precise role of adenosine in the pathogenesis of asthma and developing appropriate subtype selective agonists/antagonists represents an exciting opportunity for the development of novel therapeutics for the treatment of asthma.

References.

Brown RA, Spina D, Page CP. Adenosine receptors and asthma. Br J Pharmacol. 2008 Mar;153 Suppl 1:S446-56