Magnesium ion augmentation of inhibitory effects of adenosine on dopamine release in the rat striatum.
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 mumol/L adenosine, non-selective adenosine agonist, as well as 0.1 mumol/L 2-chloro-N6-cyclopentyladenosine (CCPA), selective adenosine A1 agonist, showed no effect on dopamine release. However, from 5 to 50 mumol/L adenosine and from 0.1 to 1 mumol/L CCPA plus Mg2+ (1 and 40 mumol/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 mumol/L of 8-cyclopentyl-1,3-dimethylxanthine (CPT), a selective adenosine A1 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 A1 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.
Okada
M
M
Department of Neuropsychiatry, Hirosaki-University, Japan.
Mizuno
K
K
Okuyama
M
M
Kaneko
S
S
D000241:Adenosine / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004357:Drug Synergism; D008274:Magnesium / Q000494:pharmacology* / Q000502:physiology; D017551:Microdialysis; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D015220:Calcium Channels; D018492:Dopamine Antagonists; D018047:Receptors, Purinergic P1; D008274:Magnesium; D000241:Adenosine; D004298:Dopamine