Clonidine inhibition of potassium-evoked release of glutamate and aspartate from rat cortical synaptosomes.
Release of endogenous glutamic acid (Glu), aspartic acid (Asp) and gamma-aminobutyric acid (GABA) has been investigated using synaptosomes prepared from rat cerebral cortex. Exposure in superfusion to a depolarizing concentration of KCl (30 mM) evoked 3-, 2- and 2-fold increases in Glu, Asp and GABA release, respectively. More than 70% of Glu and Asp overflow were calcium-dependent, although 67% of the GABA overflow was calcium-independent. Clonidine inhibited the K(+)-evoked overflow of Glu and Asp in a concentration-dependent manner, but the GABA overflow was not inhibited. Clonidine inhibited K(+)-evoked Glu and Asp overflow to 40 and 30% of the control with a potency (IC50) of 11 and 36 nM, respectively. Similarly, norepinephrine inhibited the K(+)-evoked overflow of Glu and Asp, although phenylephrine and isoproterenol showed no effect. Rauwolscine, yohimbine and idazoxan counteracted the effects of clonidine on Glu and Asp overflow. The data suggest that the depolarization-evoked overflow of excitatory amino acids is regulated in an inhibitory fashion by alpha 2 adrenoceptors, which are located on the nerve terminals of Glu and Asp neurons in rat cortex.
Kamisaki
Y
Y
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Hamahashi
T
T
Okada
C M
CM
Itoh
T
T
D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D019329:Idazoxan; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004146:Dioxanes; D005971:Glutamates; D015016:Yohimbine; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D003000:Clonidine; D011188:Potassium; D019329:Idazoxan