P2 receptors in satellite glial cells in trigeminal ganglia of mice

Abstract

There is strong evidence for the presence of nucleotide (P2) receptors in sensory neurons, which might play a role in the transmission of pain signals. In contrast, virtually nothing is known about P2 receptors in satellite glial cells (SGCs), which are the main glial cells in sensory ganglia. We investigated the possibility that P2 receptors exist in SGCs in murine trigeminal ganglia, using Ca2+ imaging, patch-clamp recordings, and immunohistochemistry. We found that ATP caused an increase in intracellular Ca2+ concentration ([Ca2+]i) in SGCs. As adenosine had no effect on [Ca2+]i, and the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid largely blocked the response to ATP we conclude that P1 receptors did not contribute to the responses. We obtained the following evidence that the responses to ATP were mediated by metabotropic P2Y receptors: (i) persistence of the responses in Ca2+-free solution, (ii) inhibition of the response by cyclopiazonic acid, (iii) [Ca2+]i increases in response to the P2Y agonists uridine triphosphate, adenosine thiodiphosphate, and 2-methylthio ADP, and (iv) failure of the P2X agonist α,β-methylene ATP to elicit a response. Agonists of P2Y1 receptors and uridine triphosphate, an agonist at P2Y2 and P2Y4 receptors, induced [Ca2+]i increases suggesting that at least these P2Y receptor subtypes are present on SGCs. Using an antibody against the P2Y4 receptor, we found immunopositive SGCs. Patch-clamp recordings of SGCs did not reveal any inward current due to ATP. Therefore, there was no evidence for the activation of ionotropic P2X receptors under the present conditions.The results indicate the presence of functional nucleotide (P2Y) receptors in SGCs.