Catecholamines

Catecholamines

Epinephrine (Adrenaline) and Norepinephrine:

The major elements in the "fight or flight" response.

The response to a threat involves an acute, integrated adjustment of many complex processes in the brain, muscles, heart and liver.

Epinephrine:

1. rapidly mobilizes fatty acids as the primary fuel for muscle action in addition to increasing muscle glycogenolysis.

2. mobilizes glucose as an energy source for the brain by increasing hepatic glycogenolysis and gluconeogenesis.
3. decreases insulin release to reduce glucose up-take by muscle and adipose tissues, thus preserving it for the central nervous system.

Biosynthesis:

Sites of Synthesis:

Epinephrine: Adrenal Medulla (part of the adrenal glands at the top of the kidneys).

Norepinephrine: made in situ on sympathetic (involuntary) nerve endings (stored in vesicles in termini of axons) and in the Adrenal Medulla. NE reaches target sites via circulation.

Regulation and Release:

Degradation:

-Catecholamines, including dopamine, are rapidly catabolized by catechol O-methyl transferase (COMT) and monoamine oxidase (MAO).

-A bewildering number of degradative intermediates from catecholamines are formed.....

Receptors:

Catecholamines act through two major clases of receptors designated a- or b- adrenergic.

Each consists of 2 subclasses, i.e. a₁, a₂, b₁ and b₂.

I = Isoproteranol, a synthetic catecholamine

Physiological / Biochemical Actions Mediated Through the Various Adrenergic Receptors:

Process	a1 Receptor	a2 Receptor	b1 Receptor	b2 Receptor
CHO Metabolism	Increase Glycogenolysis (Liver)	No Effect	No Effect	Increase Glycogenolysis; Gluconeogenesis
Fat Metabolism	No Effect	Decrease Lipolysis	Increase Lipolysis	No Effect
Hormone Secretion	No Effect	Decrease Secretion of Insulin	No Effect	Increase Secretion of Insulin & Glucagon
Muscle Contraction	Smooth Muscle; Blood Vessels; Uribary Tract	Smooth Muscle; Vascular Beds; GI Relaxation	Myocardial: Increase Rate & Increase Force	Relaxation of Bronchi

Three of these receptor subgroups are coupled to the adenylate cyclase system.

Hormones that bind to b₁ and b₂ receptors activate adenylate cyclase (2nd messenger).

Hormones that bind to a₂ receptors inhibit adenylate cyclase.

Hormones that bind to a₁ receptors effect intracellular calcium concentrations.

Cyclic AMP:

Cyclic AMP Activation of Protein Kinase A:

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