Neuroscience
Online
Section I:
Cellular and Molecular Neurobiology

14. Neuropeptides and Nitric Oxide
Part 1 of 4

Neal Waxham, Ph.D.


Further Reading


go to lecture 15, part 2 go to the index of terms go to the table of contents go to the home page go to lecture 14, part 4 Introduction to Neuropeptides and Nitric Oxide

Classical neurotransmitters (e.g., glutamate and ACh) work by the directional transfer of information between presynaptic release sites and postsynaptic clusters of receptors. The process is generally well organized spatially with some, but very limited, "spill-over" of transmitter between neighboring synapses. The situation is quite different for transmission mediated by neuropeptides and nitric oxide (NO). These molecules ignore directionality of information flow and instead influence a volume of area from their point of release. This feature is loosely analogous to the release of peptide hormones into the blood stream, which can be carried to distant sites to produce their effects. For example, NO can be produced in a postsynaptic neuron and diffuse back to the presynaptic neuron or to other neighboring neurons affecting the subsequent release of transmitter. This property is termed retrograde transmission, since the signal travels in the opposite direction (post- to pre-) as compared to the classical directionality of neurotransmission.

Neuropeptides

Many neuropeptides were originally described as hormones (e.g., somatostatin and cholecystokinin), although once characterized they were subsequently also found in neurons within the CNS. Neuropeptides typically produce neuronal responses with slow onset and long duration (Figure 14.1), and every characterized neuropeptide receptor falls into the GPCR (G-protein coupled receptor) class. For comparison, Figure 14.1 shows typical responses produced by the action of a classical neurotransmitter (glutamate) acting at an ionotropic receptor and a neuropeptide. An action potential elicited in neuron 1 (in green), a glutamate releasing neuron, produces the fast (5 msec) EPSP typical of glutamate mediated synaptic transmission. In contrast, an action potential elicited in neuron 2 (purple) that releases neuropeptide produces a slow onset (5 sec to peak) and long-duration (10 sec) EPSP. These slow EPSPs are typical of neuropeptide actions since all neuropeptide receptors are G-protein coupled.

Figure 14.1

In addition, many neuropeptides do not produce an obvious electrophysiological change in the postsynaptic neuron. For example, an action potential in neuron 3 (Figure 14.1; pink) produces no response in the postsynaptic neuron even though one can confirm through other means that neuropeptides were released. However, changes have occurred in the postsynaptic neuron as revealed in the example shown in the panels labeled "C". If one first measures the glutamate response (C1) by stimulating neuron 1, a typical response is seen. Stimulation of neuron 3 produces no response (C2) as before. However, if neuron 1 is stimulated again after the stimulation of neuron 3, the EPSP measured in the postsynaptic neuron is enhanced (C3) (the original EPSP is the solid line and the EPSP following neuron 3 stimulation is the dashed line). Thus, the neuropeptide released from neuron 3 altered the postsynaptic neuron's response to another neurotransmitter. These neuropeptides are said to be neuromodulators since their effects are to potentiate or depress the effects of a second transmitter. Other examples of such heterosynaptic plasticity are described in Chapter 7, Part 2.

Classification of Peptides by Families

Neuropeptides can be grouped into families based on similarities in their amino acid sequences (Tables I and II).

Table I
Neuropeptide Families
Tachykinins: substance P, bombesin, substance
Insulins: insulin, insulin-like growth factors
Somatostatins: somatostatin, pancreatic polypeptide
Gastrins: gastrin, cholecystokinin
Opioids: opiocortins, enkephalins, dynorphin

For example, opiates are grouped as a family due to the identical amino acid sequence Tyr-Gly-Gly-Phe--(Table II) found at the N-terminus of each.

Table II
Opiate Family-Sequence Identity in Italics

Name
Amino Acid Sequence
Leu-enkephalin Tyr-Gly-Gly-Phe-Leu-OH
Met-enkephalin Tyr-Gly-Gly-Phe-Met-OH
Beta-endorphin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-
Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-
Phe-Lys-Asn-Ala-Ile-Val-Lys-Asn-Ala-
His-Lys-Gly-Gln-His-OH
Dynorphin Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-
Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln-OH

Contact the author(s) at: nba_course@uth.tmc.edu
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