ATP metabolizing enzymes ENPP1, 2 and 3 are localized in sensory neurons of rat dorsal root ganglion

  • Kentaro Nishida Kyoto Pharmaceutical University, Department of Environmental Biochemistry, Japan.
  • Yuka Nomura Kyoto Pharmaceutical University, Department of Environmental Biochemistry, Japan.
  • Kanako Kawamori Kyoto Pharmaceutical University, Department of Environmental Biochemistry, Japan.
  • Akihiro Ohishi Kyoto Pharmaceutical University, Department of Environmental Biochemistry, Japan.
  • Kazuki Nagasawa | nagasawa@mb.kyoto-phu.ac.jp Kyoto Pharmaceutical University, Department of Environmental Biochemistry, Japan.

Abstract

In dorsal root ganglion (DRG) neurons, ATP is an important neurotransmitter in nociceptive signaling through P2 receptors (P2Rs) such as P2X2/3R, and adenosine is also involved in anti-nociceptive signaling through adenosine A1R. Thus, the clearance system for adenine nucleotide/nucleoside plays a critical role in regulation of nociceptive signaling, but there is little information on it, especially ectoenzyme expression profiles in DRG. In this study, we examined expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPPs), by which ATP is metabolized to AMP, in rat DRG. The mRNA expression levels of ENPP2 were greater than those of ENPP1 and ENPP3 in rat DRGs. On immunohistochemical analysis, ENPP1, 2 and 3 were found in soma of DRG neurons. Immunopositive rate of ENPP3 was greater than that of ENPP1 and ENPP2 in all DRG neurons. ENPP3, as compared with ENPP1 and ENPP2, was expressed mainly by isolectin B4-positive cells, and slightly by neurofilament 200-positive ones. In this way, the expression profile of ENPP1, 2 and 3 was different in DRGs, and they were mainly expressed in small/medium-sized DRG neurons. Moreover, ENPP1-, 2- and 3-immunoreactivities were colocalized with P2X2R, P2X3R and prostatic acid phosphatase (PAP), as an ectoenzyme for metabolism from AMP to adenosine. Additionally, PAP-immunoreactivity was colocalized with equilibrative nucleoside transporter (ENT) 1, as an adenosine uptake system. These results suggest that the clearance system consisted of ENPPs, PAP and ENT1 plays an important role in regulation of nociceptive signaling in sensory neurons.

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Published
2018-04-09
Section
Original Papers
Supporting Agencies
Grant-in-Aid for Young Scientists (B), Japan, The Kyoto Pharmaceutical University Fund for the Promotion of Scientific Research, The Nakatomi Foundation, A grant from the MEXT-Supported Program for the Strategic Research Foundation at Private Universities
Keywords:
Ecto-nucleotide pyrophosphatase/phosphodiesterase, dorsal root ganglion, ATP, ectoenzyme, clearance system, sensory neuron.
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How to Cite
Nishida, K., Nomura, Y., Kawamori, K., Ohishi, A., & Nagasawa, K. (2018). ATP metabolizing enzymes ENPP1, 2 and 3 are localized in sensory neurons of rat dorsal root ganglion. European Journal of Histochemistry, 62(2). https://doi.org/10.4081/ejh.2018.2877