cgs-24012 and 8-cyclopentyl-1-3-dimethylxanthine

To clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5-HT) release and 5-HT reuptake activity, hippocampal extracellular 5-HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5-HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5-HT levels. Adenosine and A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), decreased extracellular 5-HT levels, whereas non-selective antagonist, caffeine, and A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased them. When 5-HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5-HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not affect 5-HT levels; however, when A1 receptor was blocked by CPT, 5-HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5-HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5-HT reuptake activity might be modulated by hippocampal A3 receptor.

Topics: Adenosine; Animals; Antihypertensive Agents; Biological Transport; Caffeine; Central Nervous System Stimulants; Fluoxetine; Hippocampus; Male; Microdialysis; Phenethylamines; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Quipazine; Rats; Rats, Wistar; Receptor, Adenosine A2A; Receptor, Adenosine A3; Receptors, Purinergic P1; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Antagonists; Theobromine; Theophylline; Vasodilator Agents

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.

Topics: Adenosine; Animals; Biogenic Monoamines; Caffeine; Carbamazepine; Central Nervous System; Central Nervous System Stimulants; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Hippocampus; Magnesium; Male; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Rats; Rats, Wistar; Receptors, Purinergic P1; Serotonin; Theobromine; Theophylline; Visual Cortex

The effect of adenosine and related compounds on the proliferation of cultured TM4 cells, a Sertoli-like cell line, has been examined. Adenosine, as well as A1 and A2 adenosine receptor agonists (cyclohexyladenosine and N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine) inhibited cell proliferation. These effects were prevented by 8-cyclopentyl theophylline, 1,3-dimethyl-propargylxanthine and caffeine, antagonists at the A1, A2 and both receptors, respectively. The xanthines had no effect by themselves and, consistent with this, the bathing medium was found not to contain detectable levels of adenosine. It is concluded that TM4 cell proliferation can be regulated by receptors for adenosine.

Topics: Adenosine; Animals; Caffeine; Cell Division; Cells, Cultured; Male; Mice; Purinergic P1 Receptor Antagonists; Purines; Receptors, Purinergic P1; Sertoli Cells; Theobromine; Theophylline

Adenosine is released in the brain in significant quantities in response to increased cellular activity. Adenosine has been shown either to decrease synaptic transmission or to produce an excitatory response in hippocampal synapses, resulting in increased glutamate release. Previous reports have shown that adenosine or its analogs reduced Ca2+ current in dorsal root ganglion and hippocampal neurons. Here we show that the selective activation of adenosine receptor subtypes has different effects on Ca2+ channels from acutely isolated pyramidal neurons from the CA3 region of guinea pig hippocampus. Activation of A1 receptors inhibited primarily N-type Ca2+ current. In contrast, activation of A2b receptors resulted in significant potentiation of P-type but not N-type Ca2+ current. This potentiation could be inhibited by blocking the cAMP-dependent protein kinase. Because of the ubiquity of adenosine, the differential effects on Ca2+ channels of adenosine receptor subtype activation may have significant implications for neuronal excitability.

Topics: Adenosine; Animals; Calcium Channels; Cyclic AMP; Electric Conductivity; Electrophysiology; Guinea Pigs; Hippocampus; Neurons; omega-Conotoxins; Peptides, Cyclic; Protein Kinase Inhibitors; Protein Kinases; Receptors, Purinergic; Theophylline