Effects of antidepressants on P2X7 receptors.
Antidepressants including paroxetine, fluoxetine and desipramine are commonly used for treating depression. P2×7 receptors are member of the P2X family. Recent studies indicate that these receptors may constitute a novel potential target for the treatment of depression. In the present study, we examined the action of these antidepressants on cloned rat P2×7 receptors that were stably expressed in human embryonic kidney (HEK) 293 cells by using the whole-cell patch-clamp technique, and found that paroxetine at a dose of 10µM could significantly reduce the inward currents evoked by the P2×7 receptors agonist BzATP by pre-incubation for 6-12 but not by acute application (10µM) or pre-incubation for 2-6h at a dose of 1µM, 3µM or 10µM paroxetine. Neither fluoxetine nor desipramine had significant effects on currents evoked by BzATP either applied acutely or by pre-incubation at various concentrations. These results suggest that the sensitivity of rat P2×7 receptors to antidepressants is different, which may represent an unknown mechanism by which these drugs exert their therapeutic effects and side effects.
Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China. Electronic address: weiwangwf@163.com.
Wei
W
Wang
Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai 200433, China.
Zheng-Hua
ZH
Xiang
Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China.
Chun-Lei
CL
Jiang
Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China.
Wei-Zhi
WZ
Liu
Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China.
Zhi-Lei
ZL
Shang
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003866:Depressive Disorder; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D017374:Paroxetine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects* / Q000378:metabolism
D000928:Antidepressive Agents; D010975:Platelet Aggregation Inhibitors; D058486:Receptors, Purinergic P2X7; D005473:Fluoxetine; D017374:Paroxetine; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D003891:Desipramine
Antidepressants; Fluoxetine, desipramine; Human embryonic kidney cell; P2×7; Paroxetine