Neuropeptides

A neuropeptide is a peptide, a molecule formed by sequential linking of amino acids in a genetically defined order. A peptide joined to other peptide units or that has adopted secondary structure is a protein. Neuropeptides are made by neurons (nerve cells in the brain), but the term refers to peptides secreted from the nerve terminal upon stimulation. Over 100 different neuropeptides are known to be released by different populations of neurons in mammalian central and peripheral nervous systems. Many neuropeptides, particularly those made in the brain and in nerves associated with the gastrointestinal tract, have important roles in controls of food intake and energy expenditure, and are therefore relevant to the regulation of body weight and adiposity.

Neurons use chemical signals to communicate information, including neurotransmitters, neuropeptides, and even gases. Neurotransmitters and neuropeptides are distinguishable by chemical content, site of synthesis, and general effects of neural communication.

Whereas neurotransmitters are made in nerve terminals by enzyme actions on simple precursor molecules, and packaged into small vesicles locally, neuropeptides are made in the cell body. They are encoded by sequences of DNA (deoxyribonucleic acid), transcribed to mRNA (messenger-ribonucleic acid), and translated into an amino acid sequence (peptide). Because the neuropeptide is to be secreted, it is initiated by a short sequence of amino acids that permits packaging into large vesicles that are transported from the cell body down to the terminal. Sometimes the mature neuropeptide arises from a pre-propeptide that is cleaved and otherwise processed after translation. Beta-endorphin and alpha-melanocyte-stimulating hormone, both from proopiomelanocortin (POMC), are good examples.

Upon vesicle fusion with the plasma membrane at the nerve terminal, the neurotransmitter or neuropeptide is released into the space, called a synapse, between the terminal and the next cell (neuron, or other type). Neurotransmitters generally interact with receptors that contain ion channels on the postsynaptic membrane, affecting the cell's excitability by depolarizing or hyperpolarizing the plasma membrane. Neuropeptides have more diverse effects, including altering cell excitability, gene expression of other peptides, local blood flow, cell morphology, and other features and processes. Whereas neurotranmitters usually have short-term effects, neuropeptides tend to have prolonged action. Generally, neuropeptides act at receptors that are coupled to G-proteins, and affect the activity of specific enzyme cascades that lead to gene expression and other changes. These “metabotropic” receptors have subtypes that are expressed on select populations of neurons or other cells. Neuropeptides can thus act as specific signals between one population of neurons and another. Neurons often make both a neurotransmitter and one or more neuropeptides, which are released [Page 494]differentially. Neuropeptides are often associated with specific behaviors. For example, neuropeptide Y (NPY) is a neuropeptide that acts in certain brain regions to increase the organism's food intake.