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Dual effect of (−)‐N 6 ‐phenylisopropyl adenosine on guinea‐pig trachea
Author(s) -
Caparrotta L.,
Cillo F.,
Fassina G.,
Gaion R.M.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb10115.x
Subject(s) - adenosine , chemistry , adenosine receptor , contraction (grammar) , arachidonic acid , purinergic receptor , theophylline , histamine , medicine , histaminergic , endocrinology , agonist , guinea pig , muscle contraction , pharmacology , receptor , biochemistry , biology , enzyme
1 The effect of (−)‐N 6 ‐phenylisopropyl adenosine (PIA), a metabolically stable P 1 ‐receptor agonist, was investigated on guinea‐pig isolated trachea. 2 PIA showed two opposite effects: contraction, evident at low concentrations (10 −7 to 2–5 × 10 −6 m ), and relaxation at higher doses. 3 Relaxation by PIA was antagonized in an apparently competitive manner by two antagonists of extracellular (P 1 ) adenosine receptors: theophylline (Theo) and 8‐phenyltheophylline (PT). 4 Contraction by PIA was not inhibited by methylxanthines and was not mediated by stimulation of cholinergic or histaminergic systems. 5 Inhibitors of arachidonic acid cascade acting at different levels, i.e. indomethacin, nordihyd‐roguaiaretic acid (NDGA) and BW755C, all inhibited the contraction by PIA, while they potentiated the relaxation in a concentration‐dependent manner. Mepacrine, an inhibitor of phospholipase A 2 , inhibited the contraction by PIA, but did not affect the relaxation. 6 These results indicate that the contractile effect induced by PIA is supported by an indirect mechanism involving the release of arachidonic acid derivatives (via P 2 ‐purinoceptor?). Thus the balance between the two opposite effects of adenosine on tracheal tone is possibly modulated by the prostaglandin turnover.