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alpha2A-adrenoceptor stimulation reduces capsaicin-induced glutamate release from spinal cord synaptosomes.
J Pharmacol Exp Ther. 2001 Dec; 299(3):939-44.JP

Abstract

Glutamate (Glu) is involved in excitatory neurotransmission and nociception and plays an essential role in relaying noxious stimuli in the spinal cord. Intrathecal or epidural injection of alpha2-adrenergic agonists produces potent antinociceptive effects, alters spinal neurotransmitter release, and effectively treats acute nociceptive and chronic neuropathic pain. Although it is generally believed that alpha2-adrenergic receptor stimulation reduces excitatory neurotransmitter release from peripheral afferents, the subtype of receptor causing this effect and its specificity to nociceptive neurotransmission have been inadequately studied. We therefore examined the pharmacology of adrenergic agents to inhibit Glu release in spinal cord from stimulation with capsaicin, a specific agonist for receptors on nociceptive afferents. Capsaicin evoked Glu release in synaptosomes from normal rat dorsal spinal cord in a concentration-dependent manner. Glu release from 30 microM capsaicin was inhibited by adrenergic agonists with a relative potency of clonidine = dexmedetomidine > norepinephrine > ST91 >> phenylephrine = 0, consistent with an action on alpha2A/D subtype receptors. Also consistent with this interpretation was the observation that inhibition of capsaicin-induced Glu release by clonidine or dexmedetomidine was blocked by the alpha2A/D antagonist BRL44408 but not by the alpha2B/C-preferring antagonist ARC239. Similar results were obtained in perfused spinal cord slices. These data suggest that capsaicin-evoked Glu release, likely reflecting stimulation of C fiber terminals, can be inhibited by activation of the alpha2A/D subtype, and this action of adrenergic agonists may reflect in part their efficacy in the treatment of acute pain.

Authors+Show Affiliations

Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11714880

Citation

Li, X, and J C. Eisenach. "Alpha2A-adrenoceptor Stimulation Reduces Capsaicin-induced Glutamate Release From Spinal Cord Synaptosomes." The Journal of Pharmacology and Experimental Therapeutics, vol. 299, no. 3, 2001, pp. 939-44.
Li X, Eisenach JC. Alpha2A-adrenoceptor stimulation reduces capsaicin-induced glutamate release from spinal cord synaptosomes. J Pharmacol Exp Ther. 2001;299(3):939-44.
Li, X., & Eisenach, J. C. (2001). Alpha2A-adrenoceptor stimulation reduces capsaicin-induced glutamate release from spinal cord synaptosomes. The Journal of Pharmacology and Experimental Therapeutics, 299(3), 939-44.
Li X, Eisenach JC. Alpha2A-adrenoceptor Stimulation Reduces Capsaicin-induced Glutamate Release From Spinal Cord Synaptosomes. J Pharmacol Exp Ther. 2001;299(3):939-44. PubMed PMID: 11714880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - alpha2A-adrenoceptor stimulation reduces capsaicin-induced glutamate release from spinal cord synaptosomes. AU - Li,X, AU - Eisenach,J C, PY - 2001/11/21/pubmed PY - 2002/1/5/medline PY - 2001/11/21/entrez SP - 939 EP - 44 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 299 IS - 3 N2 - Glutamate (Glu) is involved in excitatory neurotransmission and nociception and plays an essential role in relaying noxious stimuli in the spinal cord. Intrathecal or epidural injection of alpha2-adrenergic agonists produces potent antinociceptive effects, alters spinal neurotransmitter release, and effectively treats acute nociceptive and chronic neuropathic pain. Although it is generally believed that alpha2-adrenergic receptor stimulation reduces excitatory neurotransmitter release from peripheral afferents, the subtype of receptor causing this effect and its specificity to nociceptive neurotransmission have been inadequately studied. We therefore examined the pharmacology of adrenergic agents to inhibit Glu release in spinal cord from stimulation with capsaicin, a specific agonist for receptors on nociceptive afferents. Capsaicin evoked Glu release in synaptosomes from normal rat dorsal spinal cord in a concentration-dependent manner. Glu release from 30 microM capsaicin was inhibited by adrenergic agonists with a relative potency of clonidine = dexmedetomidine > norepinephrine > ST91 >> phenylephrine = 0, consistent with an action on alpha2A/D subtype receptors. Also consistent with this interpretation was the observation that inhibition of capsaicin-induced Glu release by clonidine or dexmedetomidine was blocked by the alpha2A/D antagonist BRL44408 but not by the alpha2B/C-preferring antagonist ARC239. Similar results were obtained in perfused spinal cord slices. These data suggest that capsaicin-evoked Glu release, likely reflecting stimulation of C fiber terminals, can be inhibited by activation of the alpha2A/D subtype, and this action of adrenergic agonists may reflect in part their efficacy in the treatment of acute pain. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/11714880/alpha2A_adrenoceptor_stimulation_reduces_capsaicin_induced_glutamate_release_from_spinal_cord_synaptosomes_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11714880 DB - PRIME DP - Unbound Medicine ER -