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Adenosine receptors in rat basophilic leukaemia cells: transductional mechanisms and effects on 5‐hydroxytryptamine release
Author(s) -
Abbracchio Maria P.,
Paoletti Anna M.,
Luini Alberto,
Cattabeni Flaminio,
Matteis M. Antonietta
Publication year - 1992
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.1476-5381.1992.tb14266.x
Subject(s) - adenosine , adenosine receptor , adenosine a1 receptor , adenosine a2b receptor , cyclase , medicine , chemistry , adenosine a3 receptor , endocrinology , stimulation , receptor , adenylate kinase , adenosine deaminase , biology , biochemistry , agonist
1 The presence of adenosine receptors linked to adenylate cyclase activity and their functional role in calcium‐evoked 5‐hydroxytryptamine (5‐HT) release was investigated in rat basophilic leukaemia (RBL) cells, a widely used model for studying the molecular mechanisms responsible for stimulus‐secretion coupling. 2 In [ 3 H]‐5‐HT‐loaded cells triggered to release by the calcium ionophore A23187, a biphasic modulation of 5‐HT secretion was induced by adenosine analogues, with inhibition of stimulated release at n m and potentiation at μ m concentrations, suggesting the presence of adenosine receptor subtypes mediating opposite effects on calcium‐dependent release. This was also confirmed by results obtained with other agents interfering with adenosine pharmacology, such as adenosine deaminase and the non‐selective A 1 /A 2 antagonist 8‐phenyl‐theophylline. 3 Similar biphasic dose‐response curves were obtained with a variety of adenosine analogues on basal adenylate cyclase activity in RBL cells, with inhibition and stimulation of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) production at n m and μ m concentrations, respectively. The rank order of potency of adenosine analogues for inhibition and stimulation of adenylate cyclase activity and the involvement of G‐proteins in modulation of cyclic AMP levels suggested the presence of cyclase‐linked A 1 high‐affinity and A 2 ‐like low‐affinity adenosine receptor subtypes. However, the atypical antagonism profile displayed by adenosine receptor xanthine antagonists on cyclase stimulation suggested that the A 2 ‐like receptor expressed by RBL cells might represent a novel cyclase‐coupled A 2 receptor subtype. 4 Micromolar concentrations of adenosine analogues could also increase inositol phospholipid hydrolysis and inositol tris‐phosphate formation in both unstimulated cells and in cells triggered to release by the calcium ionophore. The stimulation was constant, small and additive to that exerted by the calcium ionophore. 5 It is concluded that RBL cells express both A 1 and A 2 ‐like adenosine receptors which exert opposite effects on 5‐HT release and intracellular cyclic AMP levels. However, besides modulation of cyclic AMP levels, additional transduction pathways, such as modulation of phospholipase C activity, may contribute to the release response evoked by adenosine analogues in this cell‐line.