During states of stress or anxiety, norepinephrine and epinephrine are released and bind to adrenergic receptors throughout the body which exert effects such as dilating pupils and bronchioles, increasing heart rate and constricting blood vessels, increasing renin secretion from the kidneys, and inhibiting peristalsis. ![]() One major role it is involved in is the body’s “fight or flight” response. The noradrenergic system has various functions throughout the central and peripheral nervous systems. The hormones act on alpha- and beta-adrenergic receptors of smooth muscle cells and adipose tissue located throughout the body. The sympathetic nervous system and neuroendocrine chromaffin cells (located in the adrenal medulla) are primarily responsible for the synthesis and exocytosis of norepinephrine and other catecholamines into the blood circulation. ![]() The VNB originates from nuclei in the pons and medulla and sends projections to innervate the amygdala, hypothalamus, and areas of the midbrain and medulla. It sends projections to innervate the cerebral cortex, hippocampus, and cerebellum exclusively and has projections that overlap with projections from the VNB to innervate areas of the amygdala, hypothalamus, and spinal cord. It functions as the predominant site of norepinephrine production in the central nervous system. The DNB originates from A6 locus coeruleus, located in the dorsal pons, and is composed of primarily noradrenergic neurons. The central noradrenergic system is composed of two primary ascending projections that originate from the brainstem: The dorsal noradrenergic bundle (DNB), and the ventral noradrenergic bundle (VNB). The release of these hormones into the bloodstream is stimulated by acetylcholine (released from preganglionic splanchnic fibers) which binds nicotinic receptors located in the adrenal medulla. Norepinephrine can be released into the bloodstream or be converted to epinephrine by phenylethanolamine-N-methyl transferase. Once synthesized, they get stored in chromaffin granules. In the peripheral nervous system, chromaffin cells in the adrenal medulla (following the same steps as mentioned above) synthesize norepinephrine. Phenylalanine is another amino acid that can also be used for catecholamine synthesis after it is converted to tyrosine by phenylalanine hydroxylase. Norepinephrine can then be released from the presynaptic terminal to the synaptic cleft via exocytosis or convert to epinephrine in neurons that contain the enzyme phenylethanolamine-N-methyl transferase. ![]() ![]() Dopamine gets transported into a vesicle through vesicular monoamine transporter (VMAT) where it can be converted to norepinephrine by neurons that contain an additional enzyme, dopamine beta-hydroxylase. DOPA is then decarboxylated by L-amino acid decarboxylase to produce dopamine. Tyrosine is first hydroxylated to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase (rate-limiting step). The steps for norepinephrine synthesis are as follows: Elevated levels of tyrosine in the central nervous system (CNS) triggers the production of norepinephrine and other catecholamines. Tyrosine is an aromatic amino acid that can cross the blood-brain barrier and be transported into neurons in the presynaptic terminal, where it serves as a precursor for catecholamine synthesis.
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