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Differential modulation of ATP‐induced calcium signalling by A1 and A2 adenosine receptors in cultured cortical astrocytes
Author(s) -
Alloisio Susanna,
Cugnoli Carlo,
Ferroni Stefano,
Nobile Mario
Publication year - 2004
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 - 10.1038/sj.bjp.0705707
Subject(s) - adenosine , p2y receptor , purinergic receptor , pertussis toxin , agonist , adenosine receptor , receptor , astrocyte , biology , endocrinology , medicine , purinergic signalling , microbiology and biotechnology , chemistry , biochemistry , g protein , central nervous system
Despite the accumulating evidence that under various pathological conditions the extracellular elevation of adenine‐based nucleotides and nucleosides plays a key role in the control of astroglial reactivity, how these signalling molecules interact in the regulation of astrocyte function is still largely elusive. The action of the nucleoside adenosine in the modulation of the intracellular calcium signalling ([Ca 2+ ] i ) elicited by adenosine 5′‐triphosphate (ATP)‐induced activation of P2 purinoceptors was investigated on neocortical type‐1 astrocytes in primary culture by using single‐cell microfluorimetry. Astrocyte challenge with ATP (1–10 μ M ) elicited biphasic [Ca 2+ ] i responses consisting of an initial peak followed by a sustained elevation. The stable adenosine analogue 2‐chloroadenosine (2‐ClA) potentiated the transient [Ca 2+ ] i rise induced by activation of metabotropic P2Y receptors. Among the various P1 receptor agonists tested, the nonselective agonist 5′‐ N ‐ethylcarboxamidoadenosine (NECA) mimicked the 2‐ClA action, whereas the selective A1 R(−) N6‐(2‐phenylisopropyl)‐adenosine (R‐PIA), the A2A 2‐[4‐(2‐carboxyethyl)phenethylamino]‐5′‐ N ‐ethylcarboxamidoadenosine (CGS‐21680) and A3 1‐deoxy‐1‐(6‐[([3‐lodophenyl]methyl)‐amino]‐9H‐purin‐9‐yl)‐ N ‐methyl‐ β ‐ D ‐ribofuranuronamide (IB‐MECA) agonists were ineffective. Application of R‐PIA>NECA2‐ClA depressed the [Ca 2+ ] i plateau reversibly. Moreover, in the presence of R‐PIA or 2‐ClA, the prolonged [Ca 2+ ] i signal was maintained by application of the A1 antagonist 1,3‐diethyl‐8‐phenylxanthine (DPX). Finally, preincubation of the astrocytes with pertussis toxin abrogated the 2‐ClA inhibition of the ATP‐elicited sustained [Ca 2+ ] i rise without affecting the transient [Ca 2+ ] i potentiation. Taken together, these findings indicate that stimulation of A1 and A2 adenosine receptors mediates a differential modulation of [Ca 2+ ] i signalling elicited by P2 purinoceptors. Since variations in [Ca 2+ ] i dynamics also affect cell proliferation and differentiation, our data suggest that tuning of the extracellular levels of adenosine may be relevant for the control of astrogliosis mediated by adenine nucleotides.British Journal of Pharmacology (2004) 141 , 935–942. doi: 10.1038/sj.bjp.0705707