Adrenergic Transmission..Pharmacology

Synthesis

• Tyrosine is actively transported inside the presynaptic membrane.
• Inside nerve fibers, tyrosine is converted into DOPA (dihyroxy phenyl alanine) by tyrosine hydroxylase. This is the rate limiting step.
• DOPA is converted into dopamine by decarboxylase enzyme.

Storage

• Dopamine is shifted inside storage vesicles. Here, it is converted into Nor-Epinephrine by Dopamine β hydroxylase. This enzyme is present in storage vesicles.
• Outside vesicles, MAO (mono amine oxidase) metabolizes dopamine.
• Nor-Epinephrine is converted into Epinephrine by N-Methyl Transferase.

Release

• Nor-epinephrine is released by fusion of vesicles with presynaptic membrane facilitated by calcium.
• Nor-epinephrine is released into cleft, Calcium channels open and calcium enters inside presynaptic membrane. This calcium causes fusion of vesicles with membrane.

Binding

Nor-epinephrine binds with alpha or beta receptors. Both of these are of two types;

RECEPTOR SITE THEORY OF ADRENERGIC TRANSMISSION

Two types of receptor sites are theorized to explain adrenergic effects.

Alpha-Receptors

• Alpha-receptors are associated mainly with increased contractibility of vascular smooth muscle and intestinal relaxation.

Alpha1

• The alpha1 is located at postsynaptic effector sites to stimulate transmitter release in smooth muscle. For example, the smooth muscle of peripheral blood vessels is contracted in alpha1 stimulation.

Alpha2

• The alpha2 receptor site is located presynaptic on axon terminals to inhibit the release of norepinephrine (the transmitter). The effects of alpha2 stimulation results in relaxation of the intestinal tract--motility and tone are decreased.

Beta-Receptors

• Beta-receptors are associated with vasodilation and relaxation of nonintestinal smooth muscle and cardiac stimulation.

Beta1

• Stimulation of beta1 receptor sites results in cardiac stimulation and lipolysis.

Beta2

• Stimulation of beta2 receptor sites causes bronchodilation, relaxation of blood vessels (usually in skeletal muscles), and muscle glycogenolysis.

Removal

Uptake-1

• Nor-epinephrine is actively uptaken into presynaptic membrane.

Uptake-2

• Some nor-epinephrine enters into effector cells and metabolized by MAO.