Magnesium ion augmentation of inhibitory effects of adenosine on dopamine release in the rat striatum

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Abstract
The effects of adenosine and magnesium ion (Mg2+) on striatal dopamine release were studied in awake rats by in vivo microdialysis. The mean striatal basal levels of dopamine release at Mg2+ free perfusate were 56.95 ± 5.30 fmol/sample (for 20 min). By varying the Mg2+ levels in perfusate from 0 mmol/L to 1, 10 or 40 mmol/L, the dopamine release was inhibited by Mg2+ in a level‐dependent manner. Perfusion with modified Ringer's solution containing zero Mg2+ and from 5 to 50 μmol/L adenosine, non‐selective adenosine agonist, as well as 0.1 μmol/L 2‐chloro‐N6‐cyclopentyladenosine (CCPA), selective adenosine Al agonist, showed no effect on dopamine release. However, from 5 to 50 μmol/L adenosine and from 0.1 to 1 μmol/L CCPA plus Mg2+ (1 and 40 μmol/L) perfusion decreased the dopamine release. This inhibitory effect of adenosine and CCPA on striatal dopamine release was enhanced by an increase in extracellular Mg2+ levels. Levels of 50 μmol/L of 8‐cyclopentyl‐l,3‐dimethylxanthine (CPT), a selective adenosine Al receptor antagonist, in perfusate increased the dopamine release under conditions both with and without Mg2+. This stimulatory effect of CPT on striatal dopamine release was reduced by an increase in extracellular Mg2+ levels. As a result, CPT antagonized the inhibitory effects of adenosine and CCPA on dopamine release under conditions of the presence and absence of Mg2+. These results suggest that the inhibition of striatal dopamine release by adenosine was mediated by adenosine Al receptor. This inhibition was intensified by Mg2+. This study also revealed that the concentrations of Mg2+, which ranged from physiological to supraphysiological, reduced the striatal dopamine release; furthermore it was found that the physiological concentration of Mg2+ potentiated the effects of adenosine agonists, but inhibited adenosine antagonist. Thus, the present study, using in vivo microdialysis preparations, suggests Mg2+ inhibits the calcium ion channels and enhances the adenosinergic function in the central nervous system.