P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals
| Autor: | Maria Martire, Irene Samengo, Diego Currò, Pierluigi Navarra |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Agonist
Male Purinergic P2X Receptor Antagonists Settore BIO/14 - FARMACOLOGIA medicine.drug_class lcsh:Medicine Stimulation AMPA receptor Pharmacology H]D-aspartic acid release Receptors Presynaptic Synaptic Transmission Purinergic P2X Receptor Agonists 03 medical and health sciences Glutamatergic chemistry.chemical_compound 0302 clinical medicine Trigeminal caudal nucleus medicine Animals Nociceptive circuit Receptors AMPA Receptor AMPA receptors 030304 developmental biology Nerve Endings 0303 health sciences business.industry lcsh:R Antagonist [3H]D-aspartic acid release General Medicine Central sensitization Rats Anesthesiology and Pain Medicine chemistry P2X7 receptor NBQX Neurology (clinical) Receptors Purinergic P2X7 business [ Free nerve ending Excitatory Amino Acid Antagonists 030217 neurology & neurosurgery Research Article Synaptosomes |
| Zdroj: | The Journal of Headache and Pain The Journal of Headache and Pain, Vol 21, Iss 1, Pp 1-10 (2020) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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