P(2Y) purinoceptor subtypes recruit different mek activators in astrocytes

Area of Science:

• Neuroscience
• Cellular Signaling
• Molecular Biology

Background:

• Extracellular ATP acts as a glial trophic factor and neuronal transmitter.
• Astrocytes utilize metabotropic P2Y receptors for mitogenic signaling via the extracellular signal-regulated kinase (Erk) cascade.
• The specific P2Y receptor subtypes in astrocytes and their signaling pathways to Erk remain undefined.

Purpose of the Study:

• To identify P2Y receptor subtypes expressed in rat cortical astrocytes.
• To investigate the signaling pathways linking P2Y receptors to the Erk cascade in astrocytes.
• To determine if different P2Y receptor subtypes couple to Erk via identical or distinct pathways.

Main Methods:

• Utilized P2Y receptor agonists (ATP, ADP, UTP, 2-methylthioATP) to activate Erk and MAP/Erk kinase (Mek).
• Assessed the activation of c-Raf-1, B-Raf, Mek kinase 1 (MekK1), and MekK2/3.
• Employed reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for cloned rat P2Y receptors to analyze gene expression.

Main Results:

• P2Y receptor agonists (ATP, ADP, UTP, 2MeSATP) activated Erk and Mek.
• c-Raf-1 was activated by 2MeSATP, ADP, and UTP, but not by ATP.
• Rat cortical astrocytes express P2Y(1), P2Y(2), and P2Y(4) receptor subtypes; P2Y(6) and P2Y(11) were not detected.
• Signal transduction results showed discrepancies with known recombinant P2Y receptor properties, suggesting novel native receptor functions.

Conclusions:

• Astrocytes express P2Y(1), P2Y(2), and P2Y(4) receptors, but their activation of the Erk cascade, particularly c-Raf-1, differs from expectations.
• The signaling of native P2Y receptors coupled to the Erk cascade in astrocytes may differ from recombinant receptors.
• Astrocytes might express novel purinergic or pyrimidinergic receptors involved in Erk cascade activation.