Neurotransmitters

Most neurotransmitters can be classified as amino acids, monamines (modified amino acids), or polypeptides. While more than 20 compounds have been proved to function as neurotransmitters (and the list will surely grow), some are especially prevalent through­out the nervous system and should receive individual consideration.

Acetylcholine (derived from the amino acid choline) is the neurotransmitter released at the neuromuscular junction on skeletal muscle (see Chapter 8) by some peripheral neurons of the autonomic nervous system (ANs) (discussed later) and found at many synapses throughout the central nervous system (CNs). Neurons releasing acetylcholine are classified as cholin­ergic, and this term is also applied to synapses for which acetylcholine is the neurotransmitter. Two general classes of acetylcholine (also termed cholinergic) receptors, nicotinic and muscarinic, are found at cholinergic synapses. The enzyme acetylcholinesterase is responsible for rapidly degrading acetylcholine and thus terminating its action at cholinergic synapses.

Norepinephrine is the neurotransmitter used by most peripheral neurons in the sympathetic division of the ANs (discussed later) and at synapses at several sites in the CNs. Presynap- tic neurons and synapses using norepinephrine are termed adrenergic, and this term is also applied to cell membrane receptors that bind norepinephrine. The term adrenergic has been applied to these receptors because epinephrine, or adrenaline, also binds to these receptors. (Adrenaline is the British term for epinephrine, which is released from the adrenal gland.) Adrenergic receptors may be classified as α₁, α₂, β₁, or β₂ according to their relative binding affinities for various adrenergic agonists. Epi­nephrine and norepinephrine are both classi­fied as catecholamines because of their chemical structure and because they are derived from the amino acid tyrosine.

Y-Aminobutyric acid (GABA) is the most prevalent inhibitory amino acid neurotransmit­ter in the CNs. Binding of GABA to its receptor produces neuronal hyperpolarization (inhibi­tion). Several agents that act as sedatives, tranquilizers, and general muscle relaxants have part of their effect via promoting GABA’s effects on the CNS. These include alcohol, barbiturates, and the benzodiaze­pines (e.g., diazepam and chlordiazepoxide). Some of these agents bind directly to GABA receptors; others seem to facilitate the action of endogenous GABA. The GABA receptors may also be the principal target for some general anesthetics.

Glutamate is the predominant excitatory neurotransmitter in the CNs, and several sub­types of glutamate receptors have been identi­fied. One subtype of glutamate receptor, the NMDA receptor (named for the agonist N- methyl-D-aspartate), are found in high concen­trations in areas within the brain that are involved with memory and learning. stimula­tion of NMDA receptors is believed to bring about long-term potentiation of transmission in neural pathways in these areas.