cells. Additionally, it inhibits the release of norepinephrine from adrenergic nerves. Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. There are various serotonin receptors. Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. The rate-limiting step is hydride transfer from serotonin to the flavin cofactor. There follows oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic-acid derivative. The latter is then excreted by the kidneys. Besides mammals, serotonin is found in all bilateral animals including worms and insects, as well as in fungi and in plants. Serotonin's presence in insect venoms and plant spines serves to cause pain, which is a side-effect of serotonin injection. Serotonin is produced by pathogenic amoebae, and its effect in the human gut is diarrhea. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds. Biological role Serotonin is involved in numerous physiological processes, including sleep, thermoregulation, learning and memory, pain, (social) behavior, sexual activity, feeding, motor activity, biological rhythms and possibly others. In less complex animals, such as some invertebrates, serotonin regulates feeding and other processes. In plants serotonin synthesis seems to be associated with stress signals. Cellular effects Serotonin primarily acts through its receptors and its effects depend on which cells and tissues express these receptors (see below). Receptors The 5-HT receptors, the receptors for serotonin, are located on the cell membrane of nerve cells and other cell types in animals, and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and psychedelic drugs. Except for the 5-HT3 receptor, a ligand-gated ion channel, all other 5-HT receptors are G-protein-coupled receptors (also called seven-transmembrane, or heptahelical receptors) that activate an intracellular second messenger cascade. Termination Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake, including cocaine, dextromethorphan (an antitussive), tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). A 2006 study conducted by the University of Washington suggested that a newly discovered monoamine transporter, known as PMAT, may account for "a significant percentage of 5-HT clearance". Contrasting with the high-affinity SERT, the PMAT has been identified as a low-affinity transporter, with