Serotonin (5-HT) is an ancient chemical that plays a crucial functional role in almost every living organism. It regulates platelet aggregation, activation of immune cells, and contraction of stomach and intestinal muscles. In addition, serotonin acts as a neurotransmitter in the brain and the peripheral nervous system. These activities are initiated by the binding of serotonin to 15 or more receptors that are pharmacologically classified into seven groups, 5-HT1 through 5-HT7. Each group is further divided into subgroups of receptors that are homologous but are encoded by discrete genes. With the exception of the 5-HT3 receptor-a cation channel—all of the others are G protein-coupled receptors that potentially activate or inhibit a large number of biochemical cascades. This review will endeavor to compare and contrast such signaling pathways with special attention to their tissue-specific occurrence, their possible role in immediate effects on covalent modification of other proteins, and relatively slower effects on gene expression, physiology and behavior.
Abbreviations MAPK, mitogen activated protein kinase; PI-3K, phosphoinositol-3-kinase; PTX, pertussis toxin; AcDEVD-AMC, N-acetyl-Asp-Glu-Val-Asp-(amino-4-methylcoumarin); AcDEVD-CHO, acetyl-Asp-Glu-Val-Asp-aldehyde; Ca2+/CaM, Ca2+/Calmodulin; PBS, phosphate buffered saline; MEK, MAPK kinase; 5-HT1A-R, serotonin 1A receptor; PD, PD98059; WAY, WAY100635; ERK, extracellular signal-regulated kinase; DMSO, dimethyl sulfoxide; GFX, GF109203X (bis-indolylmaleimide I); Cyt, cytochalasin D; MDC, monodansylcadaverine; Flu, Fluphenazine; PMA, phorbol myristate acetate; ER, endoplasmic reticulum; LSD, lysergic acid diethyl amide; Rsk2, p90 ribosomal protein s6 kinase; SSRI, selective serotonin reuptake inhibitor; PMSF, Phenylmethylsulfonyl fluoride; EGTA, Ethyleneglycol tetraacetic acid, gamma aminobutyric acid; EGF-R, epidermal growth factor receptor; PP2, 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo(3,4-d)pyrimidine