Monoamines as Neurotransmitters

A variety of chemicals in the CNS function as neurotransmitters. Among these are the monoamines,a chemical family that includes dopamine,norepinephrine,and serotonin. Although these molecules have similar mechanisms of action, they are used by different neurons for different functions.

The regulatory molecules epinephrine, norepinephrine, dopamine, and serotonin are in the chemical family known as monoamines. Serotonin is derived from the amino acid tryptophan. Epinephrine, norepinephrine, and dopamine are derived from the amino acid tyrosine and form a subfamily of monoamines called the catecholamines (see fig. 9.8, p. 229). Epinephrine (also called adrenaline) is a hormone secreted by the adrenal gland, not a neurotransmitter, while the closely related norepinephrine functions both as a hormone and a neurotransmitter.

Like ACh, monoamine neurotransmitters are released by exocytosis from presynaptic vesicles, diffuse across the synaptic

Chapter Seven cleft, and interact with specific receptor proteins in the membrane of the postsynaptic cell. The stimulatory effects of these monoamines, like those of ACh, must be quickly inhibited so as to maintain proper neural control. The inhibition of monoamine action is due to (1) reuptake of monoamines into the presynaptic neuron endings, (2) enzymatic degradation of monoamines in the presynaptic neuron endings by monoamine oxidase (MAO), and (3) the enzymatic degradation of catecholamines in the postsynaptic neuron by catechol-O-methyltransferase (COMT). This process is illustrated in figure 7.27.

Monoamine oxidase (MAO) inhibitors are drugs that block monoamine oxidase, the enzyme in presynaptic endings that breaks down catecholamines and serotonin after they have been taken up from the synaptic cleft. These drugs thus promote transmission at synapses that use monoamines as neurotransmitters. Such drugs have proven useful in the treatment of clinical depression, suggesting that a deficiency in monoamine transmission contributes to that disorder. An MAO inhibitor is also used to treat Parkinson's disease, because it increases the ability of dopamine to function as a neurotransmitter.

Presynaptic neuron ending

Ca2+

Action potentials

Action potentials

Ca2+

Dopa i

Dopamine

Tyrosine .1

Dopa i

Dopamine

Inactivated by MAO

/Norepinephrine m

Receptor

Reuptake (most)

Norepinephrine

Circulation a

Postsynaptic cell

Inactivated by COMT -^-Inactive products

■ Figure 7.27 The production, release, and reuptake of catecholamine neurotransmitters. The transmitters combine with receptor proteins in the postsynaptic membrane. (COMT = catechol-O-methyltransferase; MAO = monoamine oxidase.)

Fox: Human Physiology, I 7. The Nervous System: I Text Eighth Edition Neurons and Synapses

The Nervous System: Neurons and Synapses

Clinical Investigation Clues

Remember that Sandra was taking an MAO inhibitor, and that her blood levels of this drug were not unduly high. Why was Sandra taking an MAO inhibitor drug? Why might the paramedics suspect that she might have a neuromuscular disorder?

The monoamine neurotransmitters do not directly cause opening of ion channels in the postsynaptic membrane. Instead, these neurotransmitters act by means of an intermediate regulator, known as a second messenger. In the case of some synapses that use catecholamines for synaptic transmission, this second messenger is a compound known as cyclic adenosine monophosphate (cAMP). Although other synapses can use other second messengers, only the function of cAMP as a second messenger will be considered here. Other second-messenger systems are discussed in conjunction with hormone action in chapter 11.

Binding of norepinephrine, for example, with its receptor in the postsynaptic membrane stimulates the dissociation of the G-protein alpha subunit from the others in its complex (fig. 7.28). This subunit diffuses in the membrane until it binds to an enzyme known as adenylate cyclase (also called adenylyl cyclase). This enzyme converts ATP to cyclic AMP (cAMP) and pyrophosphate (two inorganic phosphates) within the postsynaptic cell cyto-

© The McGraw-Hill Companies, 2003

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