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Adenosine reduces airway excitatory non‐cholinergic (e‐NC) contraction through both A 1 and A 2 adenosine receptor activation in the guinea pig
Author(s) -
Lagente V,
Barlinski J,
Cano E,
Frossard N
Publication year - 1997
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1997.tb00853.x
Subject(s) - adenosine , agonist , adenosine receptor , adenosine a1 receptor , medicine , endocrinology , cholinergic , chemistry , guinea pig , receptor , biology
Summary— The influence of adenosine and selective A 1 and A 2 agonists and antagonists was investigated on the cholinergic and the excitatory non‐cholinergic (e‐NC) contractions induced by electrical field stimulation in the guinea‐pig bronchi. Adenosine (10 nM‐1 mM) induced a concentration‐dependent inhibition of the e‐NC contraction (EC 50 = 90 ± 14 μM), whereas the cholinergic peak was only slightly affected. Preincubation of the tissue with the adenosine uptake blocker dipyridamole (10 μM) significantly shifted the concentration‐inhibition curve to adenosine to the left (EC 50 = 10 ± 1 μM), suggesting an interaction with extracellular adenosine receptors of A 1 and/or A 2 subtype. To characterize the receptor type involved in this effect, selective adenosine derivatives were studied. The agonist to both A 1 and A 2 adenosine receptors, 5′‐N‐ethylcarboxamidoadenosine (NECA) was more potent than the selective A 1 agonist, (‐)‐R‐6‐phenylisopropyladenosine (R‐PIA), in inhibiting the e‐NC contraction (EC 50 = 0.10 ± 0.04 and 0.60 ±0.12 μM, respectively, with a maximal inhibition of 70 and 45%, respectively). The concentration‐response curve to NECA was shifted to the right by the A 2 receptor selective antagonist 3,7‐dimethyl‐1‐propargylxanthine (DMPX) (10 μM) (EC 50 = 1.4 ± 0.5 μ) as well as by the specific A 1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) (10 μM) (EC 50 = 0.7 ± 0.3 μM). The inhibitory effect induced by the association of both antagonists, DPCPX and DMPX, was considerably potentiated (EC 50 > 22 ± 2.5 μM). The effect of R‐PIA was also shifted to the right by DPCPX (EC 50 = 8.2 ± 1.6 μM) but was not modified by DMPX. The contractile response to exogenous substance P was unaffected by NECA pretreatment (0.3 μM). Altogether, these results suggest that adenosine‐induced inhibition of e‐NC contraction of guinea‐pig bronchi is mediated through activation of both A 1 and A 2 adenosine receptors linked to inhibition of the release of neuropeptides from C‐fibre nerve endings.