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Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons.
Neuropharmacology. 2015 Jun; 93:94-102.N

Abstract

Purine nucleotides, such as ATP and ADP, activate ionotropic P2X and metabotropic P2Y receptors to regulate neurotransmitter release in the peripheral as well as central nervous system. Here we report another type of ATP-induced presynaptic modulation of glutamate release in rat medullary dorsal horn neurons. Glutamatergic excitatory postsynaptic currents (EPSCs) induced by electrical stimulation of trigeminal tract were recorded from horizontal brain stem slices using a whole-cell patch clamp technique. ATP decreased the amplitude of glutamatergic EPSCs in a reversible and concentration dependent manner and increased the paired-pulse ratio. In addition, ATP reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that ATP acts presynaptically to reduce the probability of glutamate release. The ATP-induced decrease in glutamatergic EPSCs was not affected by P2X and P2Y receptor antagonists, but was completely blocked by DPCPX, a selective adenosine A1 receptor antagonist. The ATP-induced decrease in glutamatergic EPSCs was also inhibited by an inhibitor of tissue nonspecific alkaline phosphatase but not by inhibitors of other enzymes such as ecto-nucleoside triphosphate diphosphohydrolases and ecto-5'-nucleotidases. The results suggest that exogenously applied purine nucleotides are rapidly converted to adenosine by specific enzymes, and subsequently act on presynaptic A1 receptors to inhibit glutamate release from primary afferent terminals. This type of modulation mediated by purine nucleotides may play an important role in regulating nociceptive transmission from orofacial tissues.

Authors+Show Affiliations

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea.Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea. Electronic address: jis7619@knu.ac.kr.

Pub Type(s)

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

Language

eng

PubMed ID

25656480

Citation

Choi, In-Sun, et al. "Enzymatic Conversion of ATP to Adenosine Contributes to ATP-induced Inhibition of Glutamate Release in Rat Medullary Dorsal Horn Neurons." Neuropharmacology, vol. 93, 2015, pp. 94-102.
Choi IS, Cho JH, Lee MG, et al. Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons. Neuropharmacology. 2015;93:94-102.
Choi, I. S., Cho, J. H., Lee, M. G., & Jang, I. S. (2015). Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons. Neuropharmacology, 93, 94-102. https://doi.org/10.1016/j.neuropharm.2015.01.020
Choi IS, et al. Enzymatic Conversion of ATP to Adenosine Contributes to ATP-induced Inhibition of Glutamate Release in Rat Medullary Dorsal Horn Neurons. Neuropharmacology. 2015;93:94-102. PubMed PMID: 25656480.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons. AU - Choi,In-Sun, AU - Cho,Jin-Hwa, AU - Lee,Maan-Gee, AU - Jang,Il-Sung, Y1 - 2015/02/03/ PY - 2014/10/28/received PY - 2015/01/16/revised PY - 2015/01/20/accepted PY - 2015/2/7/entrez PY - 2015/2/7/pubmed PY - 2016/1/2/medline KW - ATP KW - Medullary dorsal horn KW - Patch clamp KW - Presynaptic inhibition KW - Primary afferents KW - Tissue nonspecific alkaline phosphatases SP - 94 EP - 102 JF - Neuropharmacology JO - Neuropharmacology VL - 93 N2 - Purine nucleotides, such as ATP and ADP, activate ionotropic P2X and metabotropic P2Y receptors to regulate neurotransmitter release in the peripheral as well as central nervous system. Here we report another type of ATP-induced presynaptic modulation of glutamate release in rat medullary dorsal horn neurons. Glutamatergic excitatory postsynaptic currents (EPSCs) induced by electrical stimulation of trigeminal tract were recorded from horizontal brain stem slices using a whole-cell patch clamp technique. ATP decreased the amplitude of glutamatergic EPSCs in a reversible and concentration dependent manner and increased the paired-pulse ratio. In addition, ATP reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that ATP acts presynaptically to reduce the probability of glutamate release. The ATP-induced decrease in glutamatergic EPSCs was not affected by P2X and P2Y receptor antagonists, but was completely blocked by DPCPX, a selective adenosine A1 receptor antagonist. The ATP-induced decrease in glutamatergic EPSCs was also inhibited by an inhibitor of tissue nonspecific alkaline phosphatase but not by inhibitors of other enzymes such as ecto-nucleoside triphosphate diphosphohydrolases and ecto-5'-nucleotidases. The results suggest that exogenously applied purine nucleotides are rapidly converted to adenosine by specific enzymes, and subsequently act on presynaptic A1 receptors to inhibit glutamate release from primary afferent terminals. This type of modulation mediated by purine nucleotides may play an important role in regulating nociceptive transmission from orofacial tissues. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/25656480/Enzymatic_conversion_of_ATP_to_adenosine_contributes_to_ATP_induced_inhibition_of_glutamate_release_in_rat_medullary_dorsal_horn_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(15)00036-2 DB - PRIME DP - Unbound Medicine ER -