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P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals.
J Headache Pain. 2020 Jul 02; 21(1):83.JH

Abstract

BACKGROUND

Purine receptors play roles in peripheral and central sensitization and are associated with migraine headache. We investigated the possibility that ATP plays a permissive role in the activation of AMPA receptors thus inducing Glu release from nerve terminals isolated from the rat trigeminal caudal nucleus (TCN).

METHODS

Nerve endings isolated from the rat TCN were loaded with [3H]D-aspartic acid ([3H]D-ASP), layered into thermostated superfusion chambers, and perfused continuously with physiological medium, alone or with various test drugs. Radioactivity was measured to assess [3H]D-ASP release under different experimental conditions.

RESULTS

Synaptosomal [3H]D-ASP spontaneous release was stimulated by ATP and to an even greater extent by the ATP analogue benzoylbenzoylATP (BzATP). The stimulation of [3H]D-ASP basal release by the purinergic agonists was prevented by the selective P2X7 receptor antagonist A438079. AMPA had no effect on basal [3H]D-ASP release, but the release observed when synaptosomes were exposed to AMPA plus a purinoceptor agonist exceeded that observed with ATP or BzATP alone. The selective AMPA receptor antagonist NBQX blocked this "excess" release. Co-exposure to AMPA and BzATP, each at a concentration with no release-stimulating effects, evoked a significant increase in [3H]D-ASP basal release, which was prevented by exposure to a selective AMPA antagonist.

CONCLUSIONS

P2X7 receptors expressed on glutamatergic nerve terminals in the rat TCN can mediate Glu release directly and indirectly by facilitating the activation of presynaptic AMPA receptors. The high level of glial ATP that occurs during chronic pain states can promote widespread release of Glu as well as can increase the function of AMPA receptors. In this manner, ATP contributes to the AMPA receptor activation involved in the onset and maintenance of the central sensitization associated with chronic pain.

Authors+Show Affiliations

Institute of Pharmacology, School of Medicine, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.Institute of Pharmacology, School of Medicine, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.Institute of Pharmacology, School of Medicine, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.Institute of Pharmacology, School of Medicine, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy. maria.martire@unicatt.it.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32615921

Citation

Currò, Diego, et al. "P2X7 Receptors Exert a Permissive Effect On the Activation of Presynaptic AMPA Receptors in Rat Trigeminal Caudal Nucleus Glutamatergic Nerve Terminals." The Journal of Headache and Pain, vol. 21, no. 1, 2020, p. 83.
Currò D, Navarra P, Samengo I, et al. P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals. J Headache Pain. 2020;21(1):83.
Currò, D., Navarra, P., Samengo, I., & Martire, M. (2020). P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals. The Journal of Headache and Pain, 21(1), 83. https://doi.org/10.1186/s10194-020-01153-y
Currò D, et al. P2X7 Receptors Exert a Permissive Effect On the Activation of Presynaptic AMPA Receptors in Rat Trigeminal Caudal Nucleus Glutamatergic Nerve Terminals. J Headache Pain. 2020 Jul 2;21(1):83. PubMed PMID: 32615921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals. AU - Currò,Diego, AU - Navarra,Pierluigi, AU - Samengo,Irene, AU - Martire,Maria, Y1 - 2020/07/02/ PY - 2020/03/12/received PY - 2020/06/29/accepted PY - 2020/7/4/entrez PY - 2020/7/4/pubmed PY - 2020/7/4/medline KW - AMPA receptors KW - Central sensitization KW - Nociceptive circuit KW - P2X7 receptor KW - Synaptosomes KW - Trigeminal caudal nucleus KW - [3H]D-aspartic acid release SP - 83 EP - 83 JF - The journal of headache and pain JO - J Headache Pain VL - 21 IS - 1 N2 - BACKGROUND: Purine receptors play roles in peripheral and central sensitization and are associated with migraine headache. We investigated the possibility that ATP plays a permissive role in the activation of AMPA receptors thus inducing Glu release from nerve terminals isolated from the rat trigeminal caudal nucleus (TCN). METHODS: Nerve endings isolated from the rat TCN were loaded with [3H]D-aspartic acid ([3H]D-ASP), layered into thermostated superfusion chambers, and perfused continuously with physiological medium, alone or with various test drugs. Radioactivity was measured to assess [3H]D-ASP release under different experimental conditions. RESULTS: Synaptosomal [3H]D-ASP spontaneous release was stimulated by ATP and to an even greater extent by the ATP analogue benzoylbenzoylATP (BzATP). The stimulation of [3H]D-ASP basal release by the purinergic agonists was prevented by the selective P2X7 receptor antagonist A438079. AMPA had no effect on basal [3H]D-ASP release, but the release observed when synaptosomes were exposed to AMPA plus a purinoceptor agonist exceeded that observed with ATP or BzATP alone. The selective AMPA receptor antagonist NBQX blocked this "excess" release. Co-exposure to AMPA and BzATP, each at a concentration with no release-stimulating effects, evoked a significant increase in [3H]D-ASP basal release, which was prevented by exposure to a selective AMPA antagonist. CONCLUSIONS: P2X7 receptors expressed on glutamatergic nerve terminals in the rat TCN can mediate Glu release directly and indirectly by facilitating the activation of presynaptic AMPA receptors. The high level of glial ATP that occurs during chronic pain states can promote widespread release of Glu as well as can increase the function of AMPA receptors. In this manner, ATP contributes to the AMPA receptor activation involved in the onset and maintenance of the central sensitization associated with chronic pain. SN - 1129-2377 UR - https://www.unboundmedicine.com/medline/citation/32615921/P2X7_receptors_exert_a_permissive_effect_on_the_activation_of_presynaptic_AMPA_receptors_in_rat_trigeminal_caudal_nucleus_glutamatergic_nerve_terminals L2 - https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-020-01153-y DB - PRIME DP - Unbound Medicine ER -
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