title: Presynaptic alpha 2 adrenoceptors inhibit glutamate release from rat spinal cord synaptosomes.
abstract: The presynaptic regulation of amino acid release from nerve terminals was investigated using synaptosomes prepared from the rat spinal cord. The basal releases of endogenous glutamate (Glu), aspartate (Asp), and gamma-amino-butyric acid (GABA) were 34.6, 21.5, and 10.0 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCl (30 mM) evoked 2.7-, 1.5-, and 2.9-fold increases in Glu, Asp, and GABA release, respectively. Clonidine reduced the K(+)-evoked overflow of Glu to 56% of the control overflow with a potency (IC50) of 17 nM, but it did not affect K(+)-evoked overflow of Asp, GABA, and their basal releases. Similarly, noradrenaline inhibited the K(+)-evoked overflow of Glu, although phenylephrine and isoproterenol showed no effect. The inhibitory effect of clonidine was counteracted by alpha 2-adrenoceptor antagonists, rauwolscine, yohimbine, and idazoxan, regardless of the imidazoline structures. Because Glu is considered a neurotransmitter of primary afferents that transmit both nociceptive and nonnociceptive stimuli in the spinal cord, these data suggest that part of Glu release may be regulated by the noradrenergic system through alpha 2 adrenoceptors localized on the primary afferent terminals.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kamisaki
authors.forename: T
authors.initials: T
authors.lastname: Hamada
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: M
authors.initials: M
authors.lastname: Ishimura
authors.forename: T
authors.initials: T
authors.lastname: Itoh
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D005971:Glutamates; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D007545:Isoproterenol; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine