Serotonin 5-HT7 receptors coupled to induction of interleukin-6 in human microglial MC-3 cells

Brain serotonin 5-HT7 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 (pEC(50) values) was 5-CT (7.09) > 5-HT (6.13) >= 5-MeOT (5.78) >> S-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 (pA(2) 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 mu M) and this effect was fully blocked by the 5-HT7 receptor antagonist SB-269970 (1 mu M). These data show that functional 5-HT7 receptors are present in human microglial MC-3 cells. suggesting that they are involved in neuroinflammatory processes. (c) 2005 Elsevier Ltd. All rights reserved.