Chapter 7

After studying this chapter, you should be able to:

• List the major types of neurotransmitters.
• Summarize the steps involved in the biosynthesis, release, action, and removal from the synaptic cleft of the major neurotransmitters.
• Describe the various types of receptors for amino acids, acetylcholine, monoamines, ATP, opioids, nitric oxide, and cannabinoids.
• Identify the endogenous opioid peptides, their receptors, and their functions.

Nerve endings have been called biological transducers that convert electrical energy into chemical energy. An observation made by Otto Loewi, a German pharmacologist, in 1920 serves as the foundation for the concept of chemical neurotransmission and his receipt of the Nobel Prize in Physiology and Medicine. He provided the first decisive evidence that a chemical messenger was released by the vagus nerve supplying the heart to reduce heart rate. The experimental design came to him in a dream on Easter Sunday of that year. He awoke from the dream, jotted down notes, but the next morning they were indecipherable. The next night, the dream recurred and he went to his laboratory at 3:00 AM to conduct a simple experiment on a frog heart. He isolated the hearts from two frogs, one with and one without its innervation. Both hearts were attached to cannulas filled with a saline solution. The vagus nerve of the first heart was stimulated, and then the saline solution from that heart was transferred to the noninnervated heart. The rate of its contractions slowed as if its vagus nerve had been stimulated. Loewi called the chemical released by the vagus nerve vagusstoff. Not long after, it was identified chemically to be acetylcholine. Loewi also showed that when the sympathetic nerve of the first heart was stimulated and its effluent was passed to the second heart, the rate of contraction of the “donor” heart increased as if its sympathetic fibers had been stimulated. These results proved that nerve terminals release chemicals that cause the modifications of cardiac function that occur in response to stimulation of its nerve supply.

Regardless of the type of chemical mediator involved, several common steps comprise the process of transmission at a chemical synapse. The first steps are the synthesis of the neurotransmitter usually within the nerve terminal and its storage within synaptic vesicles. This is followed by release of the chemical into the synaptic cleft in response to nerve impulses. The secreted neurotransmitter can then act on receptors on the membrane of the postsynaptic neuron, effector organ (eg, muscle or gland), or even on the presynaptic nerve terminal. The final steps in the process lead to termination of the actions of the neurotransmitter and include diffusion away from the synaptic cleft, reuptake into the nerve terminal, and enzymatic degradation. All of these processes, plus the events in the postsynaptic neuron, are regulated by many physiologic factors and can be altered by drugs. Therefore, pharmacologists (in theory) should be able to develop drugs that regulate not only somatic and visceral motor ...

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