Norepinephrine synthesis, storage, release, reuptake, metabolism.epinephrine, Dopamine. Adrenergic

01.01.2019
The Autonomic Nervous System involuntarily modifies the activity of smooth muscles, exocrine glands, cardiac tissue, and certain metabolic activities. The autonomic nervous system consists of sympathetic and parasympathetic divisions. Activation of the sympathetic system produces the “fight or flight” reaction in response to threatening situations. In this reaction, cardiovascular stimulation provides muscles with oxygen and fuels required to support vigorous physical activity, while activation of glycogenolysis and lipolysis releases the necessary energy substrates. The parasympathetic system is sometimes called the “rest and digest” system, because it slows the heart rate and promotes more vegetative functions, such as digestion, defecation, and micturition. The sympathetic nervous system consists of thoracic and lumbar nerves with short preganglionic and long postganglionic fibers. The sympathetic system includes the adrenal medulla, which releases norepinephrine and epinephrine into the blood. The Norepinephrine is principal neuro transmitters of sympathetic postganglionic fiber. Almost every step in the Norepinephrine synthesis, storage, release, reuptake/metabolism, and action of Dopamine, epinephrine, and norepinephrine can be usefully modulated by pharmacological agents. Especially for the treatment of hypertension and mental disorders like anxiety, depression and Parkinsonism. Today we will study synthesis, storage, release, reuptake/metabolism, and action Of Norepinephrine (NE). The first step of synthesis of Norepinephrine is transportation of amino acid Tyrosine into the noradrenergic nerve terminal by a sodium-dependent carrier. Tyrosine transported into the nerve is converted to dopa by enzyme tyrosine hydroxylase. Dopamine is than synthesized from dopa by action of an enzyme dopa decarboxylase. The further conversion take place in vesicles. So the Dopamine is transported into the vesicle by the vesicular monoamine transporter (VMAT). The conversion of Dopamine to Norepinephrine, is take place in the storage vesicle by enzyme dopamine-β- hydroxylase. The vesicle filled with norepinephrine, Release the Norepinephrine when an action potential opens voltage-sensitive calcium channels and increases intracellular calcium. The vesicles storing norepinephrine Fuses with the surface membrane of nerve terminal and releases the norepinephrine. After release, norepinephrine binds to its receptors that are located postsynaptic that is β1, β2, β3 and α1 and presynaptic α2 receptor. The presynaptic α2 receptor is act as an auto receptor and produce feedback inhibition of release of norepinephrine. Some norepinephrine is transported back to the cytoplasm of the varicosities by the norepinephrine transporter (NET). This process is called as reuptake. Norepinephrine also diffuse out of the cleft and metabolized—by mono amine oxidase MAO and catechol-O-methyltransferase (COMT).

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