A1 Adenosine Receptor Activation Inhibits P2X3 Receptor–Mediated ATP Currents in Rat Dorsal Root Ganglion Neurons

Autor: Jia-Wei Hao, Wen-Long Qiao, Qing Li, Shuang Wei, Xue-Mei Li, Ting-Ting Liu, Chun-Yu Qiu, Wang-Ping Hu
Rok vydání: 2022
Předmět:
Zdroj: Molecular Neurobiology. 59:7025-7035
ISSN: 1559-1182
0893-7648
Popis: Purinergic signaling plays an important role in multiple pain processes. P2X3 receptor is considered to be a target in pain therapeutics, and A1 adenosine receptor signaling is essential for analgesia. However, it is still unclear whether there is a link between A1 adenosine receptors and P2X3 receptors in pain process. Herein, we show that the A1 adenosine receptor agonist N6-cyclopentyladenosine (CPA) suppressed α,β-methylene-ATP (α,β-meATP)-evoked inward currents mediated by P2X3 receptors in a concentration- dependent and voltage-independent manner in rat dorsal root ganglion (DRG) neurons. CPA shifted the concentration-response curve for α,β-meATP downwards, with a decrease of 38.44 ± 5.87% in the maximal current response of P2X3 receptors to α,β-meATP in the presence of CPA. The CPA-induced suppression was blocked by the A1 adenosine receptor antagonist KW-3902 and prevented by intracellular application of either the Gi/o-protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, or the cAMP analog 8-Br-cAMP. CPA also suppressed the membrane excitability of DRG neurons, with a significant decrease in the amplitude of the depolarization and the number of spikes induced by α,β-meATP in the presence of CPA. Finally, intraplantar pretreatment of CPA dose-dependently relieved α,β-meATP-induced nociceptive responses in rats through peripheral A1 adenosine receptors. These results suggested that CPA suppressed the functional activity of P2X3 receptors in rat primary sensory neurons via A1 adenosine receptor, intracellular Gi/o-proteins and cAMP signaling cascades, suggesting a novel peripheral mechanism underlying its analgesic effect.
Databáze: OpenAIRE
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