Serotonine - Edubirdie

University:
The University Of Western Ontario
Course:
Biology 2290F | Scientific Method in Biology
Academic year:

2022
Views:

270

Pages:

2
Author:

Kyuwon J.

Serotonine ● Biosynthetic pathway ○ Tryptophan => Tryptophan hydroxylase => 5HTP ○ TPH isoforms ■ TPH1(peripheral) ■ TPH(neuronal CNS) ○ 5-HTP => Aromatic L- amino acid decarboxylase (AADC) > Serotonin (5-HT) ● Degradation ○ MAO-A ■ 5-HIAA = excreted through urine ● Distribution ○ CNS ■ Synthesizing raphe nuclei ■ Projects to cortex hippocampus ● Peripheral ○ Enter chromaffin cells (GI tract) ■ 90% of total 5-HT ○ Platelets ■ 5-HT is consumed through SERT release in clotting Serotonin distribution CNS ● Synthesized primarily in raphe nuclei of the brainstem ● Cerebral cortex ○ Modulation on mood + cognitions ○ Implication on depression + anxiety ● Hippocampus ● Basal ganglia (motor behaviours) ● Spinal cords - modulation in pain PNS ● Enterochromaffin cells in GI tract = produce about 90% of total serotonin ○ Regulation of intestinal motility + secretion ● Platelets ○ Not used for synthesis of serotonin ○ Uptake SERT (transporter ○ Release serotonin aids vasoconstriction + hemostasis Other ● Cardiovascular system ○ Modulation of vascular tone ● Liver , Lungs , pancreas ○ Minor effect in organ signalling Receptors ● Seven major 5_HT1 ~5-HT7 with subtubes ○ Most G-protein coupled receptors (GPCRs) ○ 5-HT3 is ion gated channels Receptor Type Function 5-HT₁A GPCR (Gi/o-coupled) Anxiolytic effect; inhibitory autoreceptor regulating serotonin release 5-HT₂A GPCR (Gq-coupled) Mediates hallucinations; causes vascular smooth muscle contraction 5-HT₃ Ligand-gated ion channel Involved in emesis and gut motility; target of antiemetics (e.g., ondansetron) 5-HT₇ GPCR (Gs-coupled) Regulates circadian rhythm and thermoregulation Clinical Relevance ● Psychiatric disorder ○ Depression anxiety OCD ○ Bipolar disorders ● Pharmacological agents ○ SSRIs blocks SERTS => increase in serotonin within the synaptic deft ○ MAO inhibitors : preventing breakdown of serotonin ○ Triptans: 5-HT1B/1D agonists used during migraine treatments ○ Antiemetics : 5JT3 antagonist used for chemotherapy causes a ● Serotonin Syndromes ○ Potentially life threatening conditions ■ Serotonergic activity ○ Hyperthermia, agitation, tremor, clonus ○ Alteration of mental status ○ Triggered through drug interactions ■ SSRI + MAOI ● Increase in SSRI = use of fluoxetine = treatment in depression , can cause serotonin syndrome once combined with other serotonin agents ● MAO-A = Phenelzine, Tranylypromine = Antidepressant effects , risk in hypertensive crisis +serotonin syndrome ● SERT inhibitions = MDMA , Cocaine = Euphoria + hyperthermia = potential for toxicity