A neurotransmitter is an endogenous chemical messenger released by a neuron to communicate with another neuron, a muscle cell, or a gland cell. At a chemical synapse, its release links activity in the sending cell to a response in the receiving cell. Neurotransmitters act through specific receptors, producing effects that range from rapid electrical changes to slower modifications of cellular activity. They are essential to communication in the brain and peripheral nervous system. (pubmed.ncbi.nlm.nih.gov)
Chemical classes
Conventional neurotransmitters fall into two broad groups: small-molecule transmitters and neuropeptides. Small-molecule transmitters include amino acids, biogenic amines, acetylcholine, and purines. Neuropeptides are chains of amino acids produced from larger precursor molecules; their actions commonly modify ongoing neuronal activity rather than generate a single brief electrical response. These categories describe chemical structure and synthesis, not an absolute division between rapid and slow signaling. (ncbi.nlm.nih.gov)
Important examples include:
- Glutamate, the principal transmitter mediating fast excitation in the mammalian central nervous system.
- Gamma-aminobutyric acid (GABA) and glycine, which commonly mediate inhibitory transmission.
- Acetylcholine, which transmits signals at skeletal neuromuscular junctions and also operates at autonomic and central synapses.
- Dopamine, involved in movement control, learning, and emotional processes.
- Serotonin, or 5-hydroxytryptamine, involved in sleep, mood, and digestion.
- Norepinephrine, also called noradrenaline, involved in alertness and autonomic regulation.
- Histamine, which participates in wakefulness as well as functions outside the nervous system. (ncbi.nlm.nih.gov)
Adenosine triphosphate (ATP) also functions as a transmitter, despite its familiar role in cellular energy transfer. A neuron need not release only one messenger: small-molecule transmitters and peptides can coexist, allowing different components of a chemical signal to produce different responses. (ncbi.nlm.nih.gov)
Synthesis, storage, and release
Many small-molecule neurotransmitters are synthesized locally in nerve terminals by enzymes that convert available precursors into the active messenger. Peptide transmitters are generally synthesized as precursor polypeptides in the cell body, processed, and transported along the axon toward release sites. These different production routes influence how transmitter supplies are replenished. (ncbi.nlm.nih.gov)
Conventional transmitters are stored in membrane-bound synaptic vesicles. An arriving action potential depolarizes the terminal and opens voltage-gated calcium channels. Calcium enters the terminal and triggers fusion of vesicles with the cell membrane, releasing their contents into the extracellular space. This mechanism converts an electrical event within a neuron into a chemical signal between cells. (pmc.ncbi.nlm.nih.gov)
Release is regulated rather than automatic in a simple all-or-nothing sense. Calcium entry, vesicle availability, and presynaptic control mechanisms influence how much transmitter is released. Transmitter molecules then move by diffusion toward accessible receptors. Some remain near a specialized synaptic contact; others reach receptors outside the immediate synaptic cleft. (pmc.ncbi.nlm.nih.gov)
Receptors and cellular effects
A neurotransmitter receptor is a protein that recognizes a transmitter and couples its binding to a cellular response. Two major receptor classes are distinguished. Ionotropic receptors are ligand-gated ion channels: transmitter binding directly changes channel opening, allowing selected ions to cross the membrane. Their responses can begin rapidly and last only milliseconds. Metabotropic receptors activate intracellular signaling pathways, often through G proteins, and usually produce slower, longer-lasting effects. (ncbi.nlm.nih.gov)
The effect of a transmitter depends on its receptor and the receiving cell. An excitatory response increases the likelihood that the cell will generate an action potential; an inhibitory response decreases it. The relevant channel properties and the concentrations of permeant ions inside and outside the cell determine the electrical outcome. Consequently, a transmitter cannot always be classified as invariably excitatory or inhibitory. Even an inhibitory response need not make the membrane potential more negative. (ncbi.nlm.nih.gov)
Transmitters also influence processes beyond immediate firing. For example, calcium entry through the NMDA receptor, a glutamate receptor, contributes to lasting changes in synaptic function associated with long-term potentiation. Such mechanisms connect chemical transmission with activity-dependent changes in neural circuits. (ncbi.nlm.nih.gov)
Signal termination and unconventional messengers
Transmission requires removal or inactivation of released messenger. Mechanisms include diffusion away from receptors, enzymatic breakdown, and uptake through membrane transporters. Uptake can return transmitter to nerve terminals or transfer it into surrounding glial cells. Different transmitters use different combinations of these mechanisms, shaping the duration and spatial extent of their signals. (pmc.ncbi.nlm.nih.gov)
Not all neuronal chemical messengers follow the vesicle-storage model. Nitric oxide is a diffusible gaseous messenger that can act on intracellular molecular targets. Endocannabinoids are another unconventional signaling group. Their inclusion illustrates that neuronal chemical communication extends beyond the classic sequence of presynaptic vesicle release followed by postsynaptic receptor activation. (pubmed.ncbi.nlm.nih.gov)
Discovery and pharmacological significance
In 1921, Otto Loewi demonstrated chemical transmission using frog hearts: fluid from a heart whose nerve had been stimulated produced a corresponding response in another heart. Henry Dale’s work helped establish acetylcholine’s role in transmission. Dale and Loewi shared the 1936 Nobel Prize in Physiology or Medicine for discoveries concerning chemical transmission of nerve impulses. (nobelprize.org)
Neurotransmitter systems are major targets in pharmacology. Drugs can activate or block receptors, alter release, or inhibit transmitter removal. Selective serotonin reuptake inhibitors, for example, act on serotonin transport. A drug’s effects therefore depend not merely on transmitter abundance but also on receptor properties, transport mechanisms, and the neural circuits in which signaling occurs. (ncbi.nlm.nih.gov)