Pharmacological interactions between magnesium ion and adenosine on monoaminergic system in the central nervous system.
The effects of magnesium ion (Mg2+), adenosine A1 and A2 receptor ligands on basal extracellular levels of striatal dopamine, hippocampal dopamine and serotonin were investigated by using in vivo microdialysis in freely moving rats. An increase in extracellular levels of Mg2+ ([Mg2+]o) reduced extracellular striatal and hippocampal monoamine levels, in a concentration dependent manner. The extracellular monoamine level was increased by perfusion with a non-selective adenosine receptor antagonist, caffeine, a selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT), and an antiepileptic drug, carbamazepine, whereas adenosine, a selective adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA) reduced extracellular monoamine levels. The former and latter were reduced and enhanced by an increase in [Mg2+]o, respectively. Neither a selective adenosine A2 agonist, N6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl) ethyl]adenosine (PD125944), nor an antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), affected extracellular monoamine levels. Under the conditions of adenosine A1 receptor blockade by CPT, adenosine, PD125944 and carbamazepine increased extracellular monoamine levels, whereas caffeine and DMPX decreased them. These stimulatory effects of adenosine, PD125944 and carbamazepine were enhanced by an increase in [Mg2+], whereas the inhibitory effects of caffeine and DMPX were reduced by Mg2+, in a concentration dependent manner. It is concluded that an activation of adenosine A1 and A2 receptors decrease and increase extracellular levels of striatal dopamine, hippocampal dopamine and serotonin, respectively. These whereas the stimulatory effects of adenosine A2 receptor on extracellular levels of monoamine are masked by the inhibitory effects of adenosine A1 receptor. In addition, an increase in [Mg2+]o enhances and reduces the effects of adenosine receptor agonists and antagonists on extracellular monoamine levels, respectively.
Okada
M
M
Department of Neuropsychiatry, Hirosaki University, Japan. okadamot@cc.hirosaki-u.ac.jp
Kaneko
S
S
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism
D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C056426:CGS 24012; D012701:Serotonin; D002220:Carbamazepine; C053907:8-cyclopentyl-1,3-dimethylxanthine; C058394:2-chloro-N(6)cyclopentyladenosine; D002110:Caffeine; C057837:3,7-dimethyl-1-propargylxanthine; D013806:Theophylline; D008274:Magnesium; D000241:Adenosine; D013805:Theobromine; D004298:Dopamine