ATP has the potential to act as a transmitter or cotransmitter at synapses in the peripheral and central nervous systems. It is found in all synaptic vesicles and is thus co-released during synaptic transmission. ATP has its own receptors, which, like standard neurotransmitters, are coupled to ion channels. Additionally, it can modify the action of other neurotransmitters it is co-released with, such as norepinephrine, serotonin, glutamate, dopamine, and GABA. Glial cells may also release ATP after certain types of stimulation. Once released, ATP is broken down by ATPases and 5-nucleotidase to adenosine, which can be taken up again by the presynaptic terminal.

Neuropeptides consist of chains of between 3 and about 40 amino acids. Research initially focused on the hypothalamus, but it is now clear that neuropeptides are released by neurons and act on receptors throughout the CNS, making them a fundamental mechanism of neurotransmission. Over 100 neuropeptides have been identified and can be classified into functional groups. Many neurons that release classic neurotransmitters also release neuropeptides, and understanding the interaction between these two types of transmitters has become an important area of research. Neuropeptides can function as the sole or primary neurotransmitter at a synapse and share similarities with classic neurotransmitters in terms of packaging into synaptic vesicles, dependence on Ca++ for release, and binding to specific receptors on target neurons. However, there are also significant differences that have led to alternative names for the intercellular communication mediated by neuropeptides, such as nonsynaptic, parasynaptic, and volume transmission.

Unlike classic neurotransmitters, neuropeptides are synthesized at the cell body and then transported to the terminal. They are packaged into large electron-dense vesicles scattered throughout the presynaptic terminal, rather than in small electron-lucent vesicles docked at the active zone where small-molecule transmitters are stored. Neuropeptide receptors are not confined to the synaptic region, and peptide action is not limited by reuptake mechanisms. These differences have functional implications and raise questions about whether the two types of transmitters are co-released or differentially released in response to particular stimulation patterns.
ATP has the potential to act as a transmitter or cotransmitter at synapses in the peripheral and central nervous systems. ATP is found in all synaptic vesicles and thus is co-released during synaptic transmission. ATP has its own receptors, which like standard neurotransmitters, are coupled to ion channels, but it can also modify the action of other neurotransmitters with which it is co-released, including norepinephrine, serotonin, glutamate, dopamine, and GABA. Glial cells may also release ATP after certain types of stimulation. Once released, ATP is broken down by ATPases and 5-nucleotidase to adenosine, which can be taken up again by the presynaptic terminal.
Peptide neurotransmitters consist of chains of between 3 and about 40 amino acids. Studies of neuropeptides
Hyperactivityofdopaminergicsynapsesmaybeinvolvedinsomeformsofpsychosis.Chlorpromazine andrelatedantipsychoticdrugsinhibitdopaminereceptorsonpostsynapticmembranesandthusdiminishtheeffectsofdopaminereleasedfrompresynapticnerveterminals.Overdosesofsuchantipsychoticdrugscanproduceatemporaryparkinsonian-likestate.
focused on the hypothalamus for many years. However, it is now clear that neuropeptides are released by neurons and act on receptors throughout the CNS and thus are a fundamental mechanism of neurotransmission throughout the CNS. To date, more than 100 neuropeptides have been identified. They can be classified into several functional groups, as shown in
Box 6.1 , which lists some of the known neuropeptides. It is now clear that many neurons that release classic neurotransmitters also release neuropeptides. As detailed later, understanding the interaction between coexisting classic and peptide transmitters has become an important area of research. In addition to being co-released with another transmitter, neuropeptides can also function as the sole or primary neurotransmitter at a synapse.
In some ways neuropeptides are like the classic neurotransmitters: they are packaged into synaptic vesicles, their release is dependent on Ca++ , and they bind to specific receptors on target neurons. However, there are also significant differences, ones that have led to alternative names for the intercellular communication mediated by neuropeptides, such as nonsynaptic, parasynaptic, and volume transmission.
Table 6.1 summarizes some of these differences between classic and peptide neurotransmitters.
Unlike classic neurotransmitters, which are synthesized at the presynaptic terminal, neuropeptides are synthesized at the cell body and then transported to the terminal (see
Fig. 6.2 ). Neuropeptides are packaged into large electron-dense vesicles that are scattered throughout the presynaptic terminal rather than in small electron-lucent vesicles docked at the active zone, where small-molecule transmitters are stored. (In neurons that make multiple neuropeptides, the various peptides are co-stored in the same vesicles.) Neuropeptide receptors are not confined to the synaptic region, and in general, peptide action is not limited by reuptake mechanisms.
Each of these differences has functional implications. For example, the separate storage of peptide and nonpeptide transmitters immediately raises the question of whether the two transmitters are co-released or differentially released in response to particular stimulation patterns.