Presynaptic inhibition by clonidine of neurotransmitter amino acid release in various brain regions.
The release of endogenous aspartic acid (Asp), glutamic acid (Glu) and gamma-aminobutyric acid (GABA) was investigated in synaptosomes prepared from various regions of the rat brain. The basal release of Asp, Glu and GABA from various regions was 12-35, 24-107 and 15-43 pmol/min per mg protein, respectively. Exposure to a depolarizing concentration of KCl (30 mM) resulted in 1.7 to 3.6-fold increases in Asp, Glu and GABA release. When clonidine (10(-4) M) was added to the perfusion medium, the K(+)-evoked overflow of both Asp and Glu was inhibited by 50-90% in the anterior cortex, thalamus and hypothalamus. Clonidine inhibited the K(+)-evoked Glu overflow by 30-40% in the posterior cortex and hippocampus. No significant effects were observed in the other brain regions (olfactory bulb, striatum, midbrain, cerebellum, pons, medulla oblongata). The inhibitory effects of clonidine were counteracted by an alpha 2-adrenoceptor antagonist, rauwolscine. The data suggest that the basal and K(+)-evoked release of Asp, Glu and GABA from nerve terminals is different in rat brain regions and that the presynaptic alpha 2-adrenoceptors which regulate the release of excitatory amino acids are mainly distributed in the anterior cerebral cortex, thalamus and hypothalamus of the rat brain.
Kamisaki
Y
Y
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Hamahashi
T
T
Hamada
T
T
Maeda
K
K
Itoh
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D005071:Evoked Potentials / Q000502:physiology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000596:Amino Acids; D005971:Glutamates; D018377:Neurotransmitter Agents; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003000:Clonidine; D011188:Potassium; D002118:Calcium