Interaction between purinoceptor subtypes on hippocampal serotonergic transmission using in vivo microdialysis.
The effects of purinoceptor subtypes on hippocampal extracellular serotonin levels were determined by using in vivo microdialysis. Perfusion with adenosine-5'-triphosphate (ATP) for 20 min produced concentration-dependent changes in hippocampal extracellular serotonin levels, which consisted of an initial rise phase, with levels increasing to 309% of control with 100 microM ATP, followed by a later rebound reduction phase, with levels decreasing to 6% of control. The P2X1-7 active P2 purinoceptor agonist, 2-methylthioATP (2-MeSATP: 100 microM) increased the extracellular serotonin level drastically (638%), while the P2X1,3 active P2 purinoceptor agonist, alpha, beta-methylene-L-ATP (alpha, beta-meATP: 100 microM) produced a small increase (132%) in the serotonin level. The P2X1,2,3,5,7 active P2 purinoceptor antagonist, suramin (100 microM), reduced the basal serotonin level (86%) and the ATP-evoked initial rise phase (from 309 to 254%) without affecting the late reduction phase. The adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT: 50 microM) potentiated the rising phase (167%) and abolished the subsequent ATP-evoked reduction phase. Perfusion with CPT and an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 10 microM), reduced the ATP-evoked initial rise (to 181%) and abolished the late reduction phases of serotonin release. These results indicate that ATP-evoked hippocampal serotonin release is composed of an initial rise phase and a later reduction phase. The ATP-evoked initial rise phase might be produced by an activation of P2X purinoceptor function, whereas the late reduction phase was modulated by the activation of adenosine A1 receptor function by adenosine, metabolized from ATP in the synaptic cleft.
Okada
M
M
Department of Neuropsychiatry, Hirosaki University, Japan. okadamot@cc.hirosaki-u.ac.jp
Kawata
Y
Y
Murakami
T
T
Wada
K
K
Mizuno
K
K
Kaneko
S
S
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D012701:Serotonin; C053907:8-cyclopentyl-1,3-dimethylxanthine; C057837:3,7-dimethyl-1-propargylxanthine; D000255:Adenosine Triphosphate; D013806:Theophylline; D013805:Theobromine; C008501:2-methylthio-ATP