Serotonin upregulates the activity of phagocytosis through 5-HT1A receptors.
1 In this study, we investigated whether serotonin could regulate the in vitro activity of phagocytosis through 5-hydroxytryptamine or serotonin (5-HT(1A)) receptors. 2 Mouse peritoneal macrophages were cultured with serotonin and the activity of phagocytosis was assessed by the uptake of zymosan and latex particles added to the culture media. Specific binding of [(3)H]8-OH-DPAT and immunohistochemistry using an affinity-purified anti-5-HT(1A)-receptor antibody were assayed in the macrophages. In addition, we took advantage of the availability of pharmacological inhibitors of nuclear factor-kappaB (NF-kappaB) to explore its role in the regulation of the 5-HT(1A) receptor. 3 Serotonin increased the in vitro activity of phagocytosis in a dose-dependent manner. The 5-HT(1A) receptor agonist (+/-)-8-hydroxy-2-(di-n-propyl-amino)-tetralin (R(+)-8-OH-DPAT) reproduced these effects. Serotonin- or R(+)-8-OH-DPAT-induced increases in phagocytosis were blocked by the 5-HT(1A) receptor antagonist WAY100635 and the NF-kappaB inhibitor pyrrolidinedithiocarbamate. Moreover, mouse peritoneal macrophages expressed specific binding sites for [(3)H]8-OH-DPAT when cultivated in the presence of zymosan or latex beads. Immunohistochemistry confirmed the expression of the 5-HT(1A) receptor protein in the macrophages. 4 These results show that serotonin can upregulate the activity of peritoneal macrophages through 5-HT(1A) receptors.
Freire-Garabal
M
M
Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine, University of Santiago de Compostela, s.n. 15782 Santiago de Compostela, A. Coruña, Spain. fffregar@usc.es
Núñez
M J
MJ
Balboa
J
J
López-Delgado
P
P
Gallego
R
R
García-Caballero
T
T
Fernández-Roel
M D
MD
Brenlla
J
J
Rey-Méndez
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007840:Latex; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D015854:Up-Regulation; D015054:Zymosan
D007840:Latex; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015054:Zymosan