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Alpha-1A adrenergic receptor Guanine nucleotide- binding protein G(q) subunit alpha Sodium- dependent noradrenaline transporter Synaptic vesicular amine transporter Voltage- dependent calcium channel subunit alpha-2/delta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent N-type calcium channel subunit alpha-1B Dopamine beta- hydroxylase Aromatic-L- amino-acid decarboxylase Tyrosine 3-monooxygenase Ca+ Norepinephrine Norepinephrine Cocaine Norepinephrine Ca+ Dopamine Ascorbic acid O2 Dehydroascorbic acid H2O L-Dopa CO2 L-Tyrosine Pyrroloquinoline quinone Copper Fe2+ Norepinephrine Alpha 1A Adrenergic Blood Vessel Relaxation Pathway Pyridoxal 5'-phosphate Cytosol Presynaptic Neuron The inhibition of norepinephrine reuptake receptors by Cocaine causes more norepinephrine to accumulate in the synapse, causing the continual activation of the alpha-2A adrenergic receptor Synapse Synaptic Vesicle Norepinephrine is produced in the locus coeruleus Cytosol Increased norepinephrine activates Alpha-2A adrenergic receptors in the blood vessels in the nose. Smooth Muscle Myocyte The increased activation of adrenergic receptors increases the contraction of smooth muscles in blood vessels which causes the blood vessels to constrict. Nose blood vessels Actin Filament Myosin Filament Myosin unbinds to actin causing muscle relaxation and vasodilation Vasodilation
ADRA1A GNAQ SLC6A2 SLC18A2 CACNA2D1 CACNA2D2 CACNA1B DBH DDC TH Calcium Norepinephrine Norepinephrine Cocaine Norepinephrine Calcium Dopamine Ascorbic acid Oxygen Dehydroascorbic acid Water L-Dopa Carbon dioxide L-Tyrosine Norepinephrine Alpha 1A Adrenergic Blood Vessel Relaxation Pathway
ADRA1A GNAQ SLC6A2 SLC18A2 CACNA2D1 CACNA2D2 CACNA1B DBH DDC TH Ca+ Norpp Norpp Cocaine Norpp Ca+ LDP VitC O2 DHAA H2O L-Dopa CO2 Tyr Pqq Cu Fe2+ PW126707 Pyr-5'P Cytosol Presynaptic Neuron The inhibition of norepinephrine reuptake receptors by Cocaine causes more norepinephrine to accumulate in the synapse, causing the continual activation of the alpha-2A adrenergic receptor Synapse Synaptic Vesicle Norepinephrine is produced in the locus coeruleus Cytosol Increased norepinephrine activates Alpha-2A adrenergic receptors in the blood vessels in the nose. Smooth Muscle Myocyte The increased activation of adrenergic receptors increases the contraction of smooth muscles in blood vessels which causes the blood vessels to constrict. Nose blood vessels Actin Filament Myosin Filament Myosin unbinds to actin causing muscle relaxation and vasodilation Vasodilation
ADRA1A GNAQ SLC6A2 SLC18A2 CACNA2D1 CACNA2D2 CACNA1B DBH DDC TH Ca2+ Norpp Norpp Cocaine Norpp Ca2+ LDP VitC O2 DHAA H2O L-Dopa CO2 Tyr PW126707