Potentiation by adenosine of histamine-induced bronchospasm in anaesthetized guinea-pig: Receptor subtype/s involved
✍ Scribed by Maria Cristina Breschi; Paola Nieri; Nicola Lazzeri; Marco Macchia
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 134 KB
- Volume
- 45
- Category
- Article
- ISSN
- 0272-4391
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✦ Synopsis
A potentiating effect by adenosine on the bronchocontractile response to histamine has been previously described in a guinea-pig model (Breschi et al. [1994] Pharmacology 49:42-51). In the present study, the subtype(s) of purinergic receptors involved in this modulatory effect of the nucleoside have been investigated. A possible role for P2 receptors or for the putative P3 receptor subtype was excluded because of the very poor modulatory effect of the P2 agonist α,β-methylene ATP when compared with the effects of all the P1 agonists tested, with the exception of 5′-N-Methyl-N6-(3-iodobenzyl)adenosine. The order of potency revealed for the P1 agonists was R-N 6 -[2-phenylisopropyl]adenosine (R-PIA) = 5′-Nmethylcarboxamidoadenosine > N 6 -2-(4-aminophenyl)ethyladenosine ≥ adenosine and in the presence of R-PIA, a significantly greater maximal effect was observed. Among the adenosine receptor antagonists evaluated, the A 2 antagonist 3,7-dimethyl-1-propargylxanthine even increased the effect of adenosine and no influence was evident with the reported A 2B antagonist enprofylline. A significant reduction of the potentiating activity of adenosine was, on the contrary, obtained with the nonselective blocker theophylline or the A 1 antagonist DPCPX. In conclusion, the above data suggest that the potentiation of histamine-induced bronchoconstriction by adenosine is mediated by the stimulation of A 1 receptors.