Abstract：
:In the rat brain, a heteromeric association between adenosine A(1) and purinergic P2Y(1) receptors has been demonstrated. It is suggested that this association plays an important role in the control of purine-mediated responses during pathophysiological conditions. Recently, we have demonstrated that these receptors colocalize on glutamatergic synaptic and astroglial membranes in rat hippocampus and reciprocally interact, thus modulating their functional responses at the G protein coupling level. In the present work, by means of immunoprecipitation studies, we demonstrated that A(1) and P2Y(1) receptors are present in human astroglial cells (ADF) and aggregate to form a multimeric complex. P2Y(1) receptor activation by its agonist, 2-methylthio-adenosine 5'-diphosphate (MeSADP), induced a time-dependent reduction in agonist-mediated A(1) receptor functional responses, causing a drop in A(1) receptor agonist potency to promote receptor-G protein coupling and to inhibit the adenylate cyclase pathway. These effects appeared to be selectively mediated by P2Y(1) receptor activation and probably occurred as a consequence of a direct receptor-receptor interaction at the plasma membrane level. These results indicated that P2Y(1) receptor activation induces A(1) receptor heterologous desensitization. The interaction between A(1) and P2Y(1) receptors may play an important role in the purinergic signaling cascade in astrocytes, which are involved in cell-to-cell communication and in control of synaptic transmission, particularly during pathological conditions, when large amounts of purines are released.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Tonazzini I,Trincavelli ML,Montali M,Martini Cdoi
10.1002/jnr.21727subject
Has Abstractpub_date
2008-10-01 00:00:00pages
2857-66issue
13eissn
0360-4012issn
1097-4547journal_volume
86pub_type
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