Neuropeptide

A neuropeptide is any of the variety of peptides found in neural tissue; e.g. endorphins, enkephalins. Now, about 100 different peptides are known to be released by different populations of neurons in the mammalian brain.

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Neurons use many different chemical signals to communicate information, including neurotransmitters, peptides, cannabinoids, and even some gases, like nitric oxide.

Many populations of neurons have distinctive biochemical phenotypes. For example, in one subpopulation of about 3000 neurons in the arcuate nucleus of the hypothalamus, three anorectic peptides are co-expressed: α-melanocyte-stimulating hormone (α-MSH), galanin-like peptide, and cocaine-and-amphetamine-regulated transcript (CART), and in another subpopulation two orexigenic peptides are co-expressed, neuropeptide Y and agouti-related peptide (AGRP). These are not the only peptides in the arcuate nucleus; β-endorphin, dynorphin, enkephalin, galanin, ghrelin, growth-hormone releasing hormone, neurotensin, neuromedin U, and somatostatin are also expressed in subpopulations of arcuate neurons. These peptides are all released centrally and act on other neurons at specific receptors. The neuropeptide Y neurons also make the classical inhibitory neurotransmitter GABA.

Peptide signals play a role in information processing that is different to that of conventional neurotransmitters, and many appear to be particularly associated with specific behaviors. For example, oxytocin and vasopressin have striking and specific effects on social behaviors, including maternal behavior and pair bonding.

Generally, peptides act at metabotropic or G-protein-coupled receptors expressed by selective populations of neurons - so peptides act as specific signals between one population of neurons and another. Neurotransmitters generally affect the excitability of other neurons, by depolarising them or by hyperpolarising them. Peptides have much more diverse effects; amongst other things, they can affect gene expression, local blood flow, synaptogenesis, and glial cell morphology. Peptides tend to have prolonged actions, and some have striking effects on behavior.

Neurons very often make both a conventional neurotransmitter (such as glutamate, GABA or dopamine) and one or more neuropeptides. Peptides are generally packaged in large dense-core vesicles, and the co-existing neurotransmitters in small synaptic vesicles. The large dense-core vesicles are often found in all parts of a neuron, including the soma, dendrites, axonal swellings and nerve endings, whereas the small synaptic vesicles are mainly found in clusters at presynaptic locations. Release of the large vesicles and the small vesicles is regulated differentially.

Examples of neuroactive peptides coexisting with other neurotransmitters

Transmitter names are shown in bold.

Norepinephrine (noradrenaline). In neurons of the A2 cell group in the nucleus of the solitary tract), norepinephrine co-exists with:

• Galanin
• Enkephalin
• Neuropeptide Y

GABA

• Somatostatin(in the hippocampus)
• Cholecystokinin
• Neuropeptide Y (in the arcuate nucleus)

Acetylcholine

• VIP
• Substance P

Dopamine

• Cholecystokinin
• Neurotensin

Epinephrine (adrenaline)

• Neuropeptide Y
• Neurotensin

Serotonin(5-HT)

• Substance P
• TRH
• Enkephalin

Some neurons make several different peptides. For instance, Vasopressin co-exists with dynorphin and galanin in magnocellular neurons of the supraoptic nucleus and paraventricular nucleus, and with CRF (in parvocellular neurons of the paraventricular nucleus)

Oxytocin in the supraoptic nucleus co-exists with enkephalin, dynorphin, cocaine-and amphetamine regulated transcript (CART) and cholecystokinin.

Diabetes Link

A new discovery might have important implications for treatment of diabetes. Researchers at the Toronto Hospital for Sick Children injected capsaicin into NOD mice (Non-obese diabetic mice, a strain that is genetically predisposed to develop the equivalent of type 1 diabetes) to kill the pancreatic sensory nerves. This treatment reduced the development of diabetes in these mice by 80%, suggesting a link between neuropeptides and the development of diabetes. When the researchers injected the pancreas of the diabetic mice with sensory neuropeptide (sP), they were cured of the diabetes for as long as 4 months. Also, insulin resistance (characteristic of type 2 diabetes) was reduced. These research results are in the process of being confirmed, and their applicability in humans will have to be established in the future. Any treatment that could result from this research is probably years away.