Presynaptic α₂ Adrenoceptors Inhibit Glutamate Release from Rat Spinal Cord Synaptosomes

Abstract

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 y-aminobutyric acid (GABA) were 34.6, 21.5, and 10.0 pmol/min/ mg of protein, respectively. Exposure to a depolarizing concentration of KCl (30 mkI) 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 (1C5J 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 a,-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 a2 adrenoceptors localized on the primary afferent terminals. The primary afferents that transmit peripheral signals to the second-order neurons in the spinal cord are differentiated by the diameters of the nerve fibers, corresponding to the conducting information. For example, pain is mediated by nociceptive nerves (A6

Noradrenergic modulation of XII motoneuron inspiratory activity does not involve α2-receptor inhibition of theIhcurrent or presynaptic glutamate release

“…For example, glutamatergic excitatory postsynaptic potentials (EPSCs) in dorsal motor vagal neurons (6), sympathetic preganglionic neurons (42), dorsal horn neurons (46), and cultured hippocampal neurons are inhibited by activation of presynaptic ␣ 2 -receptors. Clonidine also reduces the amount of glutamate that is released spontaneously from spinal synaptosomes (28) and from slices in response to capsaicin (66).…”

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal α-adrenoceptors

“…The activation of α 2 -adrenoceptors increases potassium conductance in dorsal horn neurons, which produces hyperpolarization and decreases excitability, thereby contributing to analgesia (North and Yoshimura, 1984;Ocana and Baeyens, 1993;Grudt et al, 1995). On the other hand, α 2 -adrenoceptor agonists reduce the stimulus-evoked release of substance P (Kuraishi et al, 1985;Pang and Vasko, 1986) and glutamate (Kamisaki et al, 1993;Ueda et al, 1995) in the spinal cord, thus suppressing nociceptive transmission. The locus ceruleus in the brainstem is a major cell group of catecholaminergic neurons and is known to project to the spinal cord.…”

Differential Involvement of Central and Peripheral α2 Adrenoreceptors in the Antinociception Induced by Aerobic and Resistance Exercise

“…Biochemical studies in DRG cell cultures and isolated spinal cord synaptosomes have demonstrated α2-AR agonist-mediated inhibition of stimulus-evoked SP, calcitonin gene-related peptide or glutamate release. [62][63][64] Supporting studies showing that mRNA encodes the α2A and α2C-ARs in DRG neurons after peripheral nerve injury or paw inflammation, 65,66 and another study using in vivo patch-clamp recording revealed that NE inhibited the barrage of excitatory postsynaptic potentials in rat spinal cord neurons initiated by nociceptive stimuli applied to the hindlimb. 65 Thus, the activation of α2-ARs and subsequent inhibition of primary afferent terminals is highly likely to play an important role in α2-ARs-mediated antinociception.…”