Quantitative metabolomics services for biomarker discovery and validation.
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Ca+ Tropomyosin alpha-1 chain Tropomyosin beta chain 5- hydroxytryptamine receptor 2A 5- hydroxytryptamine receptor 2B 5- hydroxytryptamine receptor 1A Voltage- depenent L-type calcium channel Voltage- depenent L-type calcium channel Voltage- depenent L-type calcium channel Ryanodine receptor 2 Sodium/calcium exchanger 1 Voltage-gated T-type calcium channel (ICaT) Voltage-gated T-type calcium channel (ICaT) 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 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 cAMP-dependent protein kinase catalytic subunit alpha Ca+ Serotonin Serotonin Methysergide Methysergide Methysergide Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ Ca+ Serotonin Methysergide L-Tryptophan Tetrahydrobiopterin O2 5-Hydroxy-L-tryptophan 4a-Hydroxytetrahydrobiopterin CO2 Na+ Na+ ATP H2O Ca+ ADP Pi Ca+ Fe2+ Pyridoxal 5'-phosphate Ca+ Troponin Troponin Muscle Relaxation GCPR signalling pathway GCPR signalling pathway Vascular endothelial cells Sarcoplasmic Reticulum Normally, calcium binding to troponin displaces tropomyosin from the myosin binding sites on the actin filaments. Low concentrations of calcium disallow this from occurring. Myosin and actin filaments slide further away from each other leading to muscle relaxation. Actin Filament Myosin Filament The 5-HT2 receptor is coupled to Methysergide and antagonizing this receptor results in the G protein signalling cascade not being activated. The G-protein signalling cascade activates protein kinase which activates calcium channels on the membrane, resulting in calcium influx. Low calcium cannot activate the ryanodine receptor on the sarcoplasmic reticulum. Cytosol Since calcium is linked to activation of muscle contraction. Reducing cytosolic calcium levels reduces muscle contraction Methysergide acts by narrowing blood vessels in the brain and reduces blood flow thereby alleviating migraine symptoms Synaptic Vesicle Cytosol Cytosol Presynaptic Neuron Postsynaptic Neuron Synapse ↓ migraine and vascular headaches Serotonin is synthesized at the raphei nuclei and stored in synaptic vesicles at the nerve terminal Methysergide is an antagonist on 5-HT2A, 5-HT2B and 5-HT2C receptors and exhibits vasoconstriction of blood vessels and agonist at 5-HT1A receptors Brain Raphei nuclei producing serotonergic neurons Blood vessel - blood brain barrier passive diffusion Methysergide is administered orally