The structure of adrenergic synapse

Adrenergic neurons release norepinephrine as the neurotransmitter. These neurons are found in the CNS and in the sympathetic nervous system where they serve as links between ganglia and the effector organs. Neurotransmission takes place at numerous beadlike enlargements called varicosities. This process involves five steps: the synthesis, storage, release, and receptor binding of the norepinephrine, followed by removal of neurotransmitter from the synaptic gap.

Tyrosine is transported into the axoplasm of the adrenergic neuron, where it is hydroxylated to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase. DOPA is decarboxylated to form dopamine. Dopamine is transported into synaptic vesicles by an amine transporter system that is also involved in the re-uptake of preformed norepinephrine.

This carrier system is blocked by drug reserpine. Dopamine is hydroxylated to form norepinephrine. Not all of the norepinephrine in vesicles, some exists in a cytoplasmic pool that can be displaced. In the adrenal medulla, norepinephrine is methylated to yield epinephrine; both are stored in chromaffin cells. On stimulation the adrenal medulla releases about 85% epinephrine and 15% norepinephrine.

Norepinephrine released from the synaptic vesicles diffuses across the synaptic space and binds to either postsynaptic receptors on the effector organ or presynaptic receptors on the nerve ending. The recognition of norepinephrine by the membrane receptors triggers a cascade of events within the cell, resulting in the formation of intracellurar second messengers that act as links in the communication between the neurotrasmitter and the action generated within the effector cell. Adrenergic receptors use both the cAMP second messenger system and the phosphoinositide cycle to transmit the signal into an effect.

Norepinephrine may diffuse out of the synaptic space; be metabolized to O-methylated derivatives by post-synaptic cell membrane-associated catechol O-methyltransferase (COMT) in the synaptic space; be recaptured by an uptake system that pulls the norepinephrine back into the neuron. The uptake by the neuronal membrane involves a sodium-potassium activated ATP-ase that can be inhibited by such drug, as cocaine, which known for you.

Part of norepinephrine reenters the cytoplasm of the adrenergic neuron and may be taken up into adrenergic vesicles. Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal mitochondria.

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