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Basic Science (24)
Author(s) -
Li Xinhui,
Zhao Zhihong,
Pan HuiLin,
Eisenach James C.,
Paqueron Xavier
Publication year - 2001
Publication title -
pain practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 58
eISSN - 1533-2500
pISSN - 1530-7085
DOI - 10.1111/j.1533-2500.2001.1011-24.x
Subject(s) - clonidine , yohimbine , idazoxan , spinal cord , receptor , adrenergic receptor , stimulation , adrenergic , pharmacology , endocrinology , norepinephrine , muscarinic acetylcholine receptor , medicine , chemistry , antagonist , prazosin , psychiatry , dopamine
Norepinephrine release from spinal synaptosomes. (Wake Forest University School of Medicine, Winston‐Salem, NC) Anesthesiology 2000;93:164–172. The purpose of this study was to determine if clonidine could inhibit release of NE in a preparation of spinal cord tissue lacking synaptic circuits. Crude synaptosomes were prepared from male Sprague‐Dawley rat spinal cord, loaded with [ 3 H]NE, and stimulated by potassium chloride to release [ 3 H]NE. Samples were incubated with clonidine in the absence or presence of various inhibitors. To study the effect of α 2A ‐adrenergic receptor subtypes, some animals were pretreated with an oligodeoxynucleotide (ODN) composed of a sense or antisense sequence to a portion of this receptor. Potassium chloride produced a concentration‐dependent increase in [ 3 H]NE release, and this release was inhibited by clonidine with a concentration producing 50% maximal inhibition (IC 50 ) of 1.3 μ m . The effect of clonidine was inhibited by the α 2A ‐adrenergic antagonists, yohimbine, and idazoxan, but not by α 1A ‐adrenergic, muscarinic, or opioid antagonists. Intrathecal pretreatment with antisense ODN to α 2A ‐adrenergic receptors reduced α 2A ‐adrenergic receptor protein expression compared with sense ODN control and also reduced clonidine‐induced inhibition of [ 3 H]NE release. Conclude that these data demonstrate the existence of classic autoinhibitory α 2A ‐adrenergic receptors in the spinal cord, probably of the α 2A subtype. They further suggest that clonidine‐induced stimulation of spinal NE release must occur from indirect actions, presumably due to activation of a spinal circuit.