Serotonin 5-HT7 receptors coupled to induction of interleukin-6 in human microglial MC-3 cells.
Brain serotonin 5-HT(7) receptors are known to be expressed in neurons and astrocytes. We now report the presence of these receptors in a third type of cell, microglial cells. 5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced concentration-dependent stimulations of cAMP accumulation in the human microglial MC-3 cell line. The maximal effect of 5-HT was 3.4+/-0.3-fold stimulation (mean+/-S.E.M., n=5) above basal levels. The rank order of agonist potency (pEC50 values) was 5-CT (7.09)>5-HT (6.13)>or=5-MeOT (5.78)>>8-OH-DPAT (ca. 5). The effect of 5-CT was inhibited in a concentration-dependent manner by the selective 5-HT7 receptor antagonist SB-269970 (pA2 value 9.03). Western blot analysis revealed the presence of immunoreactive bands corresponding to the human 5-HT7 receptor in extracts of MC-3 cells. The presence of two splice variants of the 5-HT7 receptor (5-HT7(a/b)) was visualized by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis with specific primers. In real-time PCR studies, the mRNA for interleukin-6 (IL-6) was found to be increased by 2.5-fold in MC-3 cells after 1 h incubation with 5-CT (1 microM) and this effect was fully blocked by the 5-HT7 receptor antagonist SB-269970 (1 microM). These data show that functional 5-HT7 receptors are present in human microglial MC-3 cells, suggesting that they are involved in neuroinflammatory processes.
Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, WSJ-386.7.44, CH-4002 Basel, Switzerland.
Cécile
C
Mahé
Erika
E
Loetscher
Kumlesh K
KK
Dev
Ionel
I
Bobirnac
Uwe
U
Otten
Philippe
P
Schoeffter
D008735:5-Methoxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D015850:Interleukin-6; D010636:Phenols; D012333:RNA, Messenger; D011985:Receptors, Serotonin; C404922:SB 269970; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D012701:Serotonin; D008735:5-Methoxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D000242:Cyclic AMP