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Norepinephrine release from spinal synaptosomes: auto-alpha2 -adrenergic receptor modulation.
Anesthesiology. 2000 Jul; 93(1):164-72.A

Abstract

BACKGROUND

Clonidine produces analgesia after spinal injection by activating alpha2-adrenergic receptors. Recently, clonidine has been demonstrated to increase spinal release of norepinephrine (NE) in vivo, in contrast to that anticipated by classic presynaptic autoinhibition. The purpose of the current study was to determine if clonidine could inhibit release of NE in a preparation of spinal cord tissue lacking synaptic circuits.

METHODS

Crude synaptosomes were prepared from male Sprague-Dawley rat spinal cord, loaded with [3H]NE, and stimulated by potassium chloride to release [3H]NE. Samples were incubated with clonidine in the absence or presence of various inhibitors. To study the effect of alpha2a-adrenergic receptor subtypes, some animals were pretreated with an oligodeoxynucleotide (ODN) composed of a sense or antisense sequence to a portion of this receptor.

RESULTS

Potassium chloride produced a concentration-dependent increase in [3H]NE release, and this release was inhibited by clonidine with a concentration producing 50% maximal inhibition (IC50) of 1.3 microm. The effect of clonidine was inhibited by the alpha2-adrenergic antagonists, yohimbine and idazoxan, but not by alpha1-adrenergic, muscarinic, or opioid antagonists. Intrathecal pretreatment with antisense ODN to alpha2A-adrenergic receptors reduced alpha2A-adrenergic receptor protein expression compared with sense ODN control and also reduced clonidine-induced inhibition of [3H]NE release.

CONCLUSIONS

These data demonstrate the existence of classic autoinhibitory alpha2-adrenergic receptors in the spinal cord, probably of the alpha2Asubtype. They further suggest that clonidine-induced stimulation of spinal NE release must occur from indirect actions, presumably due to activation of a spinal circuit.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

10861160

Citation

Li, X, et al. "Norepinephrine Release From Spinal Synaptosomes: Auto-alpha2 -adrenergic Receptor Modulation." Anesthesiology, vol. 93, no. 1, 2000, pp. 164-72.
Li X, Zhao Z, Pan HL, et al. Norepinephrine release from spinal synaptosomes: auto-alpha2 -adrenergic receptor modulation. Anesthesiology. 2000;93(1):164-72.
Li, X., Zhao, Z., Pan, H. L., Eisenach, J. C., & Paqueron, X. (2000). Norepinephrine release from spinal synaptosomes: auto-alpha2 -adrenergic receptor modulation. Anesthesiology, 93(1), 164-72.
Li X, et al. Norepinephrine Release From Spinal Synaptosomes: Auto-alpha2 -adrenergic Receptor Modulation. Anesthesiology. 2000;93(1):164-72. PubMed PMID: 10861160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Norepinephrine release from spinal synaptosomes: auto-alpha2 -adrenergic receptor modulation. AU - Li,X, AU - Zhao,Z, AU - Pan,H L, AU - Eisenach,J C, AU - Paqueron,X, PY - 2000/6/22/pubmed PY - 2000/8/12/medline PY - 2000/6/22/entrez SP - 164 EP - 72 JF - Anesthesiology JO - Anesthesiology VL - 93 IS - 1 N2 - BACKGROUND: Clonidine produces analgesia after spinal injection by activating alpha2-adrenergic receptors. Recently, clonidine has been demonstrated to increase spinal release of norepinephrine (NE) in vivo, in contrast to that anticipated by classic presynaptic autoinhibition. The purpose of the current study was to determine if clonidine could inhibit release of NE in a preparation of spinal cord tissue lacking synaptic circuits. METHODS: Crude synaptosomes were prepared from male Sprague-Dawley rat spinal cord, loaded with [3H]NE, and stimulated by potassium chloride to release [3H]NE. Samples were incubated with clonidine in the absence or presence of various inhibitors. To study the effect of alpha2a-adrenergic receptor subtypes, some animals were pretreated with an oligodeoxynucleotide (ODN) composed of a sense or antisense sequence to a portion of this receptor. RESULTS: Potassium chloride produced a concentration-dependent increase in [3H]NE release, and this release was inhibited by clonidine with a concentration producing 50% maximal inhibition (IC50) of 1.3 microm. The effect of clonidine was inhibited by the alpha2-adrenergic antagonists, yohimbine and idazoxan, but not by alpha1-adrenergic, muscarinic, or opioid antagonists. Intrathecal pretreatment with antisense ODN to alpha2A-adrenergic receptors reduced alpha2A-adrenergic receptor protein expression compared with sense ODN control and also reduced clonidine-induced inhibition of [3H]NE release. CONCLUSIONS: These data demonstrate the existence of classic autoinhibitory alpha2-adrenergic receptors in the spinal cord, probably of the alpha2Asubtype. They further suggest that clonidine-induced stimulation of spinal NE release must occur from indirect actions, presumably due to activation of a spinal circuit. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/10861160/Norepinephrine_release_from_spinal_synaptosomes:_auto_alpha2__adrenergic_receptor_modulation_ L2 - http://anesthesiology.pubs.asahq.org/article.aspx?volume=93&page=164 DB - PRIME DP - Unbound Medicine ER -