The synthesis, packaging, secretion, and removal of neurotransmitters. (A) The life cycle of transmitter agents entails (1) neurotransmitter synthesis, (2) packaging into vesicles, (3) fusion of vesicles resulting in neurotransmitter release, and (4) activation of postsynaptic receptors. Neurotransmitters are then removed from the synaptic cleft (5). In many cases, the neurotransmitter and/or a breakdown product is reused for neurotransmitter synthesis. (B) Small-molecule neurotransmitters are synthesized at nerve terminals. The enzymes necessary for neurotransmitter synthesis are made in the cell body of the presynaptic cell (1) and are transported down the axon by slow axonal transport (2). Precursors are taken up into the terminals by specific transporters, and neurotransmitter synthesis and packaging take place within the nerve endings (3). After vesicle fusion and release (4), the neurotransmitter may be enzymatically degraded. The reuptake of the neurotransmitter (or its metabolites) starts another cycle of synthesis, packaging, release, and removal (5). (C) Peptide neurotransmitters, as well as the enzymes that modify their precursors, are synthesized in the cell body (1). Enzymes and propeptides are packaged into vesicles in the Golgi apparatus. During fast axonal transport of these vesicles to the nerve terminals (2), the enzymes modify the propeptides to produce one or more neurotransmitter peptides (3). After vesicle fusion and exocytosis, the peptides diffuse away and are degraded by proteolytic enzymes (4).