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5- hydroxytryptamine receptor 3A Voltage- dependent P/Q-type calcium channel subunit alpha-1A Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Synaptic vesicular amine transporter Sodium- dependent serotonin transporter Tryptophan 5-hydroxylase 1 Aromatic-L- amino-acid decarboxylase Ca+ Serotonin Serotonin Palonosetron Ca+ Serotonin Palonosetron Palonosetron Palonosetron L-Tryptophan Tetrahydrobiopterin O2 5-Hydroxy-L-tryptophan 4a-Hydroxytetrahydrobiopterin CO2 Na+ Na+ Fe2+ Pyridoxal 5'-phosphate Vagus nerve stimulation Activation of emetic reflex Activation of emetic reflex Synaptic Vesicle Cytosol Cytosol Presynaptic Neuron Postsynaptic Neuron Synapse Palonosetron competitively blocks 5HT3A receptors leading to antiemetic effects Serotonin is synthesized at the raphei nuclei and stored in synaptic vesicles at the nerve terminal Serotonin (5HT3A) receptors, acting centrally in the chemoreceptor trigger zone (area postrema) is stimulated to cause nausea and vomiting Brain Raphei nuclei produces serotonergic neurons Blood vessel passive diffusion Palonosetron is administered orally or intravenously Palonosetron selectively blocks 5HT3A receptors in the chemoreceptor trigger zone centrally Chemoreceptor Trigger Zone 5HT3 receptors are also located on the vagus nerve terminals in the periphery vagus nerve senses nausea and vomiting triggers within the gastrointestinal tract (GIT), such as stomach irritants. smooth muscle of the GIT 5HT3A receptors present on vagal afferent nerve terminals are activated by serotonin released from enterochromaffin cells in the gut or by circulating emetogenic substances.
HTR3A CACNA1A CACNB1 CACNA2D2 SLC18A2 SLC6A4 TPH1 DDC Calcium Serotonin Serotonin Palonosetron Calcium Serotonin Palonosetron Palonosetron Palonosetron L-Tryptophan Tetrahydrobiopterin Oxygen 5-Hydroxy-L- tryptophan 4a- Hydroxytetrahydrobiopterin Carbon dioxide Sodium Sodium Vagus nerve stimulation Activation of emetic reflex Activation of emetic reflex