Chapter 5 Notes
* Dopamine and the related substances norepinephrine (NE) and epinephrine (EPI) comprise a small but important group of neurotransmitters and hormones called catecholamines. * Catecholamine contains two chemical similarities: a core structure of catechol and a nitrogen-containing group called an amine. The catecholamines, in turn, belong to a wider group of transmitter called either monoamines (transmitters that possess one amine group) or biogenic amines * EPI – adrenergic. NE- noradrenergic
* Varying amount of these substances are found within the CNS, PNS, and the inner part of the adrenal glands (adrenal medulla). * The adrenal medulla secretes EPI and NE into the bloodstream, where they act as hormones. * The synthesis of catecholamine neurotransmitters occurs in several steps. * The biochemical pathways begins with the amino acid tyrosine. Tyrosine comes from dietary protein that is transported from blood to brain. * Neurons that use DA as their transmitter contain only the first two enzymes: tyrosine hydroxylase (TH) and aromatic acid decarboxylase (AADC), and thus the biochemical pathway stops at DA. * In contrast, neurons that need to synthesize NE also possess the third enzyme, which is called dopamine Beta-hydroxylase (DBH) * The conversions of tyrosine to DOPA by TH occurs at a slower rate than the subsequent reactions in the biochemical pathway. TH is the rate-limiting enzyme in the pathway, because it determines the overall rate of DA or NE formation. * The activity of TH is regulated by a variety of factors, including how much DA or NE is present within the nerve terminal.
* Catecholamine formation can be increased by the administration of a biochemical precursor such as L-DOPA. * Vesicular packaging is important not only because it provides a means for releasing a predetermined amount of neurotransmitter (usually several thousand molecules per vesicles) but also because it protects the neurotransmitter from degradation by enzymes within the nerve terminal. * A specific protein in the vesicle membrane is responsible for vesicular monoamine transporter (VMAT). There are two related VMATs: VMAT1 in the adrenal medullar, where as VMAT2 is present in the brain. * Both of these vesicular transporters are blocked by an interesting drug called reserpine. * Blocking the vesicular transporter means that DA and NE are no longer protected from breakdown within the nerve terminal. As a result, both transmitters temporarily drop to very low levels in the brain causing sedation and depression symptoms. * Release of catecholamines normally occurs when a nerve impulse enters the terminal and triggers one or more vesicles to release their contents into the synaptic cleft by the process of exocytosis. * Certain drugs, however can cause a release of catecholamines independently of nerve cell firing. Amphetamine and Methamphetamine. * Catecholamines release is inhibited by autoreceptors located on the cell bodies, terminals, and dendrites of dopaminergic and noradrenergic neurons. * These autoreceptors inhibit catecholamine release by reducing the amount of Ca2+ that enters the terminal in response to a nerve impulse. * Thus, if a dopaminergic cell fires several action potentials in a row, we can imagine that DA released by the first few impulses stimulates the terminal autoreceptors and reduces the amount of DA released by the later action potentials. * On the other hand, the somatodendritic autoreceptors function in a different way. * The DA and NE systems posses a number a different subtypes of receptors. Here we will just mention that the DA autoreceptor is of the D2 receptor subtype and the NE autoreceptor is of the alpha 2 subtype. * Drugs that stimulate autoreceptors inhibit catecholamine release, just the like the neurotransmitter itself. * In contrast, autoreceptors...
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