Adrenergic Transmission

Norepinephrine (NE), dopamine (DA), and epinephrine (Epi) are catecholamines. NE is the principal transmitter of most sympathetic postganglionic fibers and of certain tracts in the CNS. DA is the predominant transmitter of the mammalian extrapyramidal system and of several mesocortical and mesolimbic neuronal pathways. Epi is the major hormone of the adrenal medulla. There are important interactions between the endogenous catecholamines and many of the drugs used in the treatment of hypertension, mental disorders, and a variety of other conditions described in subsequent chapters. The basic physiological, biochemical, and pharmacological features are presented here. Almost every step in the synthesis, storage, release, reuptake/metabolism, and action of catecholamine can be usefully modulated by pharmacological agents.

SYNTHESIS, STORAGE, AND RELEASE OF CATECHOLAMINES Synthesis—The steps in the synthesis of DA, NE (known outside the U.S. as noradrenaline), and Epi (known as adrenaline) are shown in Figure 6-4. Tyrosine is sequentially 3-hydroxylated and decarboxylated to form DA. DA is b-hydroxylated to yield NE (the transmitter in postganglionic nerves of the sympathetic branch of the ANS), which is N-methylated in chromaffin tissue to give Epi. The enzymes involved are not completely specific; consequently, other endogenous substances and some drugs are also substrates. 5-hydroxytryptamine (5-HT, serotonin) can be produced from 5-hydroxy-l-tryptophan by aromatic l-amino acid decarboxylase (AAD or dopa decarboxylase). AAD also converts dopa into DA, and methyldopa to a-methyl-DA, which is converted to a-methyl-NE by dopamine b-hydroxylase (DbH; Table 6-4).

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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