Skip to main content

P2 receptor-mediated modulation of noradrenaline release by electrical field stimulation and ischemic conditions in superfused rat hippocampus slices

In this study the regulation of the release of noradrenaline by P2 receptors was investigated in hippocampus slices preincubated with [3H]NA. Electrical field stimulation (EFS; 2 Hz, 240 shock, 1 ms) enhanced the release of noradrenaline in a [Ca]o-dependent manner. In contrast, the excess release in response to ischemic-like conditions (combined oxygen and glucose deprivation) was [Ca]o-independent. The Na+ channel blocker tetrodotoxin (1–3 μM) abolished both EFS-evoked and in vitro ischemia-evoked release of tritium. The P2 receptor agonists ATP, ADP and 2-MeSADP concentration-dependently decreased the tritium overflow with the potency order of ADP > 2-MeSADP > ATP. The inhibition by ATP (300 μM) was prevented by the P2 receptor antagonist PPADS (30 μM), by the P2Y1 receptor antagonist MRS2179 (10 μM) and by the P2Y12/13 receptor antagonist 2-MeSAMP (10 μM). Under ischemic-like conditions the P2X1 receptor antagonist PPNDS (1 μM) inhibited the outflow of [3H]NA, whereas MRS2179 (10 μM) significantly increased the tritium outflow. PPADS and 2-MeSAMP did not affect ischemia-evoked [3H]NA efflux. RT-PCR analysis revealed that mRNA encoding P2Y12 and P2Y13 receptor subunits were expressed in the brainstem including locus coeruleus. The pharmacological profile of the underlying receptor subtype resembles the P2Y1 and P2Y13 receptor phenotype, and the endogenous activation of P2X1 and P2Y1 receptors contribute to the modulation of noradrenaline efflux upon ischemic-like conditions.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Beáta Sperlágh.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Csölle, C., Heinrich, A. & Sperlágh, B. P2 receptor-mediated modulation of noradrenaline release by electrical field stimulation and ischemic conditions in superfused rat hippocampus slices. BMC Pharmacol 7, A35 (2007). https://doi.org/10.1186/1471-2210-7-S2-A35

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1471-2210-7-S2-A35

Keywords

  • P2X1 Receptor
  • Hippocampus Slice
  • P2Y1 Receptor
  • Electrical Field Stimulation
  • P2Y1 Receptor Antagonist