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Role of P2Y1 receptor in astroglia-to-neuron signaling at dorsal spinal cord.
J Neurosci Res 2009; 87(12):2667-76JN

Abstract

Several studies have shown that astrocytes release neurotransmitters into the extracellular space that may then activate receptors on nearby neurons. In the present study, the actions of adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS)-activated astrocyte conditioned medium (ADPbetaS-ACM) on cultured dorsal spinal cord neurons were evaluated by using confocal laser scanning microscopy and whole-cell patch-clamp recording. ADPbetaS caused astrocytic glutamate efflux (43 microM), which in turn induced inward currents in dorsal horn neurons with short time in culture. The inward currents were abolished by 2-amino-5-phosphonlanoicacid (AP-5; NMDAR antagonist) plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDAR antagonist) but were unaffected by MRS2179 (selective P2Y(1) receptor antagonist). Furthermore, N6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) was used to block glutamate release from astrocytes. As a result, ADPbetaS-ACM-induced inward currents in neurons were significantly blocked. On the other hand, both NMDAR and non-NMDAR were involved in ADPbetaS-ACM (concentration was diluted to one-tenth)-evoked small [Ca(2+)](i) transients in neurons. Under this condition, the values of glutamate concentrations in the medium are close to values for extracellular glutamate concentrations under physiological conditions. For this reason, it is possible that astrocyte-derived glutamate is important for distant neuron under physiological conditions at dorsal spinal cord. These observations indicate that astrocytic P2Y(1) receptor activation triggered glutamate efflux, which acts on distant neurons to elevate calcium levels or acts on nearby neurons to evoke inward current. Finally, our results support the conclusion that the astrocytic P2Y(1) receptor plays an important role in bidirectional communication between astrocytes and neurons.

Authors+Show Affiliations

Department of Neurobiology, College of Medicine, Third Military Medical University, Chongqing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19396875

Citation

Zeng, Jun-Wei, et al. "Role of P2Y1 Receptor in Astroglia-to-neuron Signaling at Dorsal Spinal Cord." Journal of Neuroscience Research, vol. 87, no. 12, 2009, pp. 2667-76.
Zeng JW, Liu XH, Zhao YD, et al. Role of P2Y1 receptor in astroglia-to-neuron signaling at dorsal spinal cord. J Neurosci Res. 2009;87(12):2667-76.
Zeng, J. W., Liu, X. H., Zhao, Y. D., Xiao, Z., He, W. J., Hu, Z. A., & Ruan, H. Z. (2009). Role of P2Y1 receptor in astroglia-to-neuron signaling at dorsal spinal cord. Journal of Neuroscience Research, 87(12), pp. 2667-76. doi:10.1002/jnr.22108.
Zeng JW, et al. Role of P2Y1 Receptor in Astroglia-to-neuron Signaling at Dorsal Spinal Cord. J Neurosci Res. 2009;87(12):2667-76. PubMed PMID: 19396875.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of P2Y1 receptor in astroglia-to-neuron signaling at dorsal spinal cord. AU - Zeng,Jun-Wei, AU - Liu,Xiao-Hong, AU - Zhao,Yan-Dong, AU - Xiao,Zhi, AU - He,Wen-Juan, AU - Hu,Zhi-An, AU - Ruan,Huai-Zhen, PY - 2009/4/28/entrez PY - 2009/4/28/pubmed PY - 2010/1/13/medline SP - 2667 EP - 76 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 87 IS - 12 N2 - Several studies have shown that astrocytes release neurotransmitters into the extracellular space that may then activate receptors on nearby neurons. In the present study, the actions of adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS)-activated astrocyte conditioned medium (ADPbetaS-ACM) on cultured dorsal spinal cord neurons were evaluated by using confocal laser scanning microscopy and whole-cell patch-clamp recording. ADPbetaS caused astrocytic glutamate efflux (43 microM), which in turn induced inward currents in dorsal horn neurons with short time in culture. The inward currents were abolished by 2-amino-5-phosphonlanoicacid (AP-5; NMDAR antagonist) plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDAR antagonist) but were unaffected by MRS2179 (selective P2Y(1) receptor antagonist). Furthermore, N6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) was used to block glutamate release from astrocytes. As a result, ADPbetaS-ACM-induced inward currents in neurons were significantly blocked. On the other hand, both NMDAR and non-NMDAR were involved in ADPbetaS-ACM (concentration was diluted to one-tenth)-evoked small [Ca(2+)](i) transients in neurons. Under this condition, the values of glutamate concentrations in the medium are close to values for extracellular glutamate concentrations under physiological conditions. For this reason, it is possible that astrocyte-derived glutamate is important for distant neuron under physiological conditions at dorsal spinal cord. These observations indicate that astrocytic P2Y(1) receptor activation triggered glutamate efflux, which acts on distant neurons to elevate calcium levels or acts on nearby neurons to evoke inward current. Finally, our results support the conclusion that the astrocytic P2Y(1) receptor plays an important role in bidirectional communication between astrocytes and neurons. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/19396875/Role_of_P2Y1_receptor_in_astroglia_to_neuron_signaling_at_dorsal_spinal_cord_ L2 - https://doi.org/10.1002/jnr.22108 DB - PRIME DP - Unbound Medicine ER -