RT Book, Section A1 Nestler, Eric J. A1 Kenny, Paul J. A1 Russo, Scott J. A1 Schaefer, Anne SR Print(0) ID 1174973756 T1 Neuropeptides T2 Nestler, Hyman & Malenka’s Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 4e YR 2020 FD 2020 PB McGraw-Hill PP New York, NY SN 9781260456905 LK neurology.mhmedical.com/content.aspx?aid=1174973756 RD 2024/10/13 AB KEY CONCEPTSNeuropeptides are small proteins or polypeptides that serve as neurotransmitters in the nervous system. Other signaling peptides such as growth factors and cytokines are considered to be distinct even though they may have some overlapping functions.Like the monoamines and acetylcholine, neuropeptide transmitters serve primarily modulatory roles in the nervous system.The synthesis of neuropeptides, like that of all proteins, requires the transcription of DNA and translation of the resulting messenger RNA (mRNA) into protein.Neuropeptides are synthesized as large precursor prepropeptides that undergo extensive posttranslational processing, which includes cleavages into smaller peptides and enzymatic modification. The “pre” refers to an N-terminal signal sequence that directs newly synthesized peptides into the regulated secretory pathway.As a result of alternative RNA splicing and differential cleavage of propeptides in different tissues, a single gene can give rise to diverse signaling peptides with distinct functions.Unlike small–molecule neurotransmitters, which are packaged in small synaptic vesicles, neuropeptides are generally packaged in large dense core vesicles; both types of vesicles may be found in the same neuron.Neuropeptides may diffuse for relatively long distances within the extracellular space before binding to their specific receptors.Neuropeptide transmitters act almost exclusively via activation of G protein–coupled receptors.Neuropeptides and their receptors modulate many diverse functions of the central nervous system, including sleep, arousal, reward, feeding, pain, cognition, stress responses, and emotions.