Definition
Neuropeptides are 3-40 amino acids in length functions as neurotransmitters. They are widespread in the central nervous system and the peripheral nervous system.
Discovery
Neuropeptides were discovered in 1975 by Dr John Hughes and Dr. Kosterlitz. They were the endorphins, the internally-produced morphine-like substances responsible for an array of drug-like effects in the body. A neuropeptide precursor mRNA sequence can be identified from sequence information 1, and the resulting translated protein sequence includes a signal peptide sequence and one or multiple neuropeptides. An extensive and complicated series of enzymatic processing steps, including cleavage by prohormone or proprotein convertases and other post-translational modifications, occur on the translated protein sequence before the active neuropeptides are created 2,3.
Structural Characteristics
Conformational properties of several like neuropeptides from mollusks were investigated by nuclear magnetic resonance (NMR) spectroscopy. Amino acid substitutions in the N-terminal variable regions of the peptides had dramatic effects on the populations of reverse turns in solution. The populations of turns, as measured by two independent NMR parameters, were found to be highly correlated (r2 = 0.93 and 0.82) with IC50 values using receptor membrane preparations from Helix aspersa. These results suggest that the conformational ensemble reduces the effective concentration of a particular peptide with respect to a particular receptor 4,5.
The neuropeptide Y is identical to the human peptide and is highly homologous to avian pancreatic polypeptide. The homology between neuropeptide Y and avian pancreatic polypeptide preserves all of the residues essential for the maintenance of the tertiary structure. Results suggest that neuropeptide preserves a compact tertiary structure characterized by extensive hydrophobic interactions between an N-terminal polyproline-II-like helix and a C-terminal a-helix 6.
Some peptides have been found via one of the many orphan receptors, that is receptors for which the endogenous ligand is unknown eg, "opioid receptor-like 1" (ORL1). Subsequently, the structure of the endogenous agonist of this ORL1 receptor, a 17-amino acid peptide termed orphanin FQ or nociceptin, have been elucidated 7.
Mode of Action
Neuropeptides are peptides released by neurons as intercellular messengers. Some neuropeptides function as neurotransmitters, and others function as hormones. Neuropeptides, can work both for and against us. Anti-inflammatory neuropeptides work for us to reduce inflammation fo the skin. Neuropeptides are created by nature to interact with target cell membrane receptor(s) in well-defined sites of action and for a very limited time. Therefore, most of these endogenous compounds are characterized by low biological barrier permeability and very high susceptibility to enzymatic degradation. Intraventricular or systemic injection of neuropeptide Y (NPY) can produce a decrease in plasma luteinizing hormone (LH) levels in castrated rats of both sexes. NPY is of physiological importance in the regulation of LH secretion in the rat and that the action of NPY could be exerted by at least two different ways: (1) a stimulatory effect of NPY on serotoninergic systems which in turn inhibit LHRH release and (2) a direct stimulatory effect of the peptide on LHRH neuronal system 6.
Functions
Biological functions, Neuropeptides control our mood, energy levels, pain and pleasure reception, body weight, and ability to solve problems; they also form memories, affective behavior, appetite, and inflammation, repair scars and wrinkles and regulate our immune system. These active little messengers in the brain actually turn on cellular function in the skin 7. Therefore, today, the design of drugs that interact with neuropeptide systems is one of the most explored avenues in postgenomic medicinal chemistry.
Substance P has been identified as a major neuropeptide responsible for transmission of nociceptive signals. Endogenous opioids are native neuropeptides that are responsible for modulation (generally, suppression) of nociceptive signals.
Immune system, when they are secreted, they activate natural killer cells (NK cells) and thereby increase our immune system.
Lesion of blood vessel, as the Endorphins are secreted more and more, the shrunken blood vessels return to a normal state allowing blood to flow in a normal manner. Most adult disease start form clogged blood vessels. Endorphins help to improve the circulation of blood.
Endorphins have anti-aging effect by removing superoxide, The oxygen coming into the body from breathing can change into a Superoxide. This is one of the biggest enemies for human causing diseases and aging.
Anti-stress hormones, the ability to cope with the stress is in proportion to the endorphins levels we have in our body.
Pain-relieving effect, our nervous system secretes neuro-transmitters when it receives the signal of pain. Once the endorphins are released at that moment of pain, endorphins combine with endorphin receptors on the neuron, which hinders the first neuro-transmitters from being secreted.
Memory, neuropeptides can improve memory as they can keep the brain cells young and healthy.
References
1. Hummon AB, Richmond TA, Verleyen P, Baggerman G, Huybrechts J, Ewing MA, Vierstraete E, Rodriguez-Zas SL, Liliane SL, Robinson GE (2006). From the genome to the proteome: uncovering peptides in the Apis brain. Science, 27(314):647-649.
2. Rockwell NC, Krysan DJ, Komiyama T, Fuller RS (2002). Precursor processing by Kex2/Furin Proteases. Chem. Rev., 102:4525–4548.
3. Von ER, Beck-Sickinger AG (2004). Biosynthesis of peptide hormones derived from precursor sequences. Curr. Med. Chem.,11:2651–2665.
4. Edison AS, Espinoza E, Zachariah C (1999). Conformational Ensembles: The Role of Neuropeptide Structures in Receptor Binding. The Journal of Neuroscience., 19(15):6318-6326.
5. Payza K, Greenberg MJ, Price DA (1989). Further characterization of Helix FMRFamide receptors: kinetics, tissue distribution, and interactions with the endogenous heptapeptides. Peptides, 10:657-661.
6. Allen J, Novotný J, Martin J, Heinrich G (1987). Molecular structure of mammalian neuropeptide Y: Analysis by molecular cloning and computer-aided comparison with crystal structure of avian homologue. PNAS., 84:2532-2536.
7. Guya J, Lia S, Pelletier G (1988). Studies on the physiological role and mechanism of action of neuropeptide Y in the regulation of luteinizing hormone secretion in the rat. Regulatory Peptides., 23(2):209-216.