6.1:
Adrenergic Neurons: Neurotransmission
Adrenergic neurons in postganglionic sympathetic fibers release NA as the principal neurotransmitter.
NA is a catecholamine derived biosynthetically from its metabolic precursor tyrosine—an amino acid transported into the neuron via a sodium-dependant carrier.
In the cytoplasm, tyrosine is enzymatically hydroxylated to DOPA, which is further decarboxylated to DA.
Through amine transporters, DA moves from the cytoplasm to the synaptic vesicles and undergoes β-hydroxylation to yield NA.
The arrival of neuronal action potential triggers Ca2+ influx into the neuronal cytoplasm leading to vesicular exocytosis, releasing NA in the synaptic space.
The released NA binds to receptors on nerve endings or effector organs. This triggers a cellular cascade and the formation of second messengers, transducing the signal into an effect.
The unused NA either diffuses into the systemic circulation, is inactivated by COMT in the synapse or undergoes neuronal reuptake. Post-reuptake, NA is either taken up by synaptic vesicles or oxidized by MAO.
6.1:
Adrenergic Neurons: Neurotransmission
Postganglionic sympathetic fibers (except those supplying the sweat glands) releasing noradrenaline or norepinephrine are called noradrenergic or adrenergic neurons. Noradrenaline, dopamine, adrenaline, or epinephrine are collectively called "catecholamines" as they contain a catechol moiety and an amine side chain. The five stages of neurotransmitter release involve their synthesis, storage, release, reuptake and metabolism.
Synthesis: Catecholamine synthesis requires tyrosine, which is taken to the neuronal cytoplasm via carrier-mediated transport. Tyrosine hydroxylase catalyzes the rate-limiting step converting tyrosine to DOPA, which is inhibited by metyrosine. DOPA is then decarboxylated to yield dopamine. Dopamine β-hydroxylase converts dopamine to noradrenaline, which is then stored in synaptic vesicles. Drugs like copper chelating agents and disulfiram inhibit dopamine β-hydroxylase. Additionally, phenylethanolamine N-methyltransferase converts noradrenaline to adrenaline in the adrenal medulla.
Storage: Synthesized noradrenaline and adrenaline are stored in vesicles in the nerve terminals and adrenal medulla via the vesicular monoamine transporter (VMAT).
Release: Upon the arrival of a nerve impulse and the subsequent calcium influx, vesicles containing noradrenaline rupture and release it into the synaptic junction. The released noradrenaline binds to and activates adrenergic receptors, resulting in effects termed the "fight-or-flight" response.
Reuptake: The action of noradrenaline is terminated by reuptake or sequestration by nearby cells. Most neuronal reuptake is performed with the help of the noradrenaline transporter, while the extraneuronal monoamine transporter performs extraneuronal uptake.
Metabolism and excretion: Catecholamines are metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). MAO converts catecholamines to aldehydes, which are further metabolized to carboxylic acids, while COMT methylates one of the catechol hydroxyl groups to a methoxy derivative. 3-methoxy-4-hydroxyphenylglycol (MHPG), the final product created by actions of MAO and COMT, undergoes partial conjugation before urinary excretion as glucuronide or sulfate derivatives.