Neuropeptides are the largest and most diverse class of signalling molecules in the brain. Neuropeptides act as neurotransmitters, as modulators of neurotransmission by other neurotransmitters, as autocrine/paracrine regulators, and as hormones. Some of the chemokines are also neuropeptides.

Classic neuropeptides are formed by enzymatic processing of gene-encoded precursor molecules. Precursors are produced mainly in neurons. Neuropeptides can be classified into families based on the genes that encode the precursor peptides. Human genome contains ∼90 genes that encode neuropeptide precursors. Many classical neuropeptides are synthesized not only in neurons but also in endocrine glands, functioning as peptide hormones. Strict definition of neuropeptides excludes peptide hormones that are not synthesized by neurons although they signal to the brain; these include insulin and leptin.

Neuropeptides, like other hormones and neurotransmitters, are stored and, by demand, secreted via regulated secretory pathways, and bind to specific G-protein coupled or metabotropic receptors on target cells. These receptors can be targeted with specific radioligands for PET imaging. Neuropeptides modulate the signalling of other neurons, but they can directly innervate non-neurons via synaptic contact in peripheral organs (Salio et al., 2006; Burbach, 2010; Merighi et al., 2011; Elphick et al., 2018).

Neuropeptide gene families the functional peptides that they encode include:

Opioid gene family

Vasopressin/oxytocin gene family

CCK/gastrin gene family

Somatostatin gene family

F- and Y-amide gene family

Calcitocin gene family

Natriuretic factor gene family

Bombesin-like peptide gene family

Endothelin gene family

Glucagon/secretin gene family

CHR-related gene family

Kinin and tensin gene family

Motilin family

Insulin family

Adipose neuropeptides

No-family neuropeptides

PET imaging

Several radiolabelled peptides have been developed targeting neuropeptide systems, for example somatostatin receptors, GLP-1 receptor, and natriuretic peptide receptor C.

See also:


Fonseca ICF, Castelo-Branco M, Cavadas C, Abrunhosa AJ. PET imaging of the neuropeptide Y system: a systematic review. Molecules 2022; 27, 3726. doi: 10.3390/molecules27123726.

Jackson IM, Scott PJH, Thompson S. Clinical applications of radiolabeled peptides for PET. Semin Nucl Med. 2017; 47(5): 493-523. doi: 10.1053/j.semnuclmed.2017.05.007.

Kastin AJ (ed.): Handbook of Biologically Active Peptides, 2nd ed., Academic Press, 2013. eISBN: 9780123850966.

Merighi A (ed.): Neuropeptides - Methods and Protocols. Springer, 2011. doi: 10.1007/978-1-61779-310-3.

Roivainen A, Jalkanen S, Nanni C. Gallium-labelled peptides for imaging of inflammation. Eur J Nucl Med Mol Imaging 2012; 39(Suppl 1): S68-S77. doi: 10.1007/s00259-011-1987-6.

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Updated at: 2023-01-16
Created at: 2017-10-28
Written by: Vesa Oikonen