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CHAPTER

7

Neurotransmitters &

Neuromodulators

OBJECTIVES

After studying this chapter, you should be able to:

■

List neurotransmitters and the principal sites in the nervous system at which they

are released.

■

Describe the receptors for catecholamines, acetylcholine, 5-HT, amino acids, and opioids.

■

Summarize the steps involved in the biosynthesis, release, action, and removal from

the synaptic cleft of the various synaptic transmitters.

■

Define opioid peptide, list the principal opioid peptides in the body, and name the

precursor molecules from which they originate.

INTRODUCTION

The fact that transmission at most synapses is chemical is of great

physiologic and pharmacologic importance. Nerve endings have

been called biological transducers that convert electrical energy

into chemical energy. In broad terms, this conversion process

involves the synthesis of the
neurotransmitters,
their storage in

synaptic vesicles, and their release by the nerve impulses into the

synaptic cleft. The secreted transmitters then act on appropriate

receptors on the membrane of the postsynaptic cell and are rap-

idly removed from the synaptic cleft by diffusion, metabolism,

and, in many instances, reuptake into the presynaptic neuron.

Some chemicals released by neurons have little or no direct

effects on their own but can modify the effects of neurotransmit-

ters. These chemicals are called

neuromodulators.

All these pro-

cesses, plus the postreceptor events in the postsynaptic neuron,

are regulated by many physiologic factors and at least in theory

can be altered by drugs. Therefore, pharmacologists (in theory)

should be able to develop drugs that regulate not only somatic

and visceral motor activity but also emotions, behavior, and all

the other complex functions of the brain.

CHEMICAL TRANSMISSION

OF SYNAPTIC ACTIVITY

CHEMISTRY OF TRANSMITTERS

One suspects that a substance is a neurotransmitter if it is un-
evenly distributed in the nervous system and its distribution
parallels that of its receptors and synthesizing and catabolizing
enzymes. Additional evidence includes demonstration that it is
released from appropriate brain regions in vitro and that it pro-
duces effects on single target neurons when applied to their
membranes by means of a micropipette (microiontophoresis).

Many transmitters and enzymes involved in their synthesis and

catabolism have been localized in nerve endings by

immuno-

histochemistry,

a technique in which antibodies to a given sub-

stance are labeled and applied to brain and other tissues. The

antibodies bind to the substance, and the location of the sub-

stance is then determined by locating the label with the light mi-

croscope or electron microscope.

In situ hybridization

histochemistry,

which permits localization of the mRNAs for

particular synthesizing enzymes or receptors, has also been a

valuable tool.

Identified neurotransmitters and neuromodulators can be

divided into two major categories: small-molecule transmitters

and large-molecule transmitters. Small-molecule transmitters