Peptide Neurotransmitters and Hormones


Neuropeptides are a structurally diverse class of chemical messengers that play important roles in the coordination of many physiological and behavioural events. Neuropeptides are derived from the cleavage of larger precursor proteins at the dibasic amino acid sites by prohormone convertases. They are synthesised in the cell body, packaged in the large dense core vesicles and released in a neuronal activity‐dependent manner. The neuropeptides may function as blood‐borne hormones or as mediators/transmitters affecting neuronal activity in the nervous system. In the target cells, neuropeptides activate the complementary G protein‐coupled receptors and elicit responses that are specific to these cells. The released peptide is subsequently inactivated by the actions of several nonspecific extracellular peptidases.

Key Concepts

  • Neuropeptides are a structurally diverse class of chemical messengers produced by nerve cells to coordinate many physiological and behavioural processes.
  • The major neuroendocrine centre in the brain is the pituitary gland.
  • Neuropeptides are derived from the cleavage of the larger precursor proteins by specific endoproteases that are copackaged in the dense core secretory granules.
  • Receptors for neuropeptides belong mainly to the family of G protein‐coupled receptor.
  • G protein‐coupled receptor may be activated in complex modes beyond their interaction with G proteins.

Keywords: peptides; biosynthesis; function; degradation; endocrine/neuronal communication

Figure 1. In situ hybridisation (ISH) of mouse brain reveals regional expression pattern of neuropeptides. The images and data are generated from Allen Brain Atlas mouse brain ISH data (http://mouse.brain‐ for (a) PACAP, (b) Cholecystokinin and (c) Oxytocin. Panels from left to right show the ISH images, the expression images and the quantified expression of the neuropeptide in each brain regions. Adapted from Allen Brain Atlas.
Figure 2. Schematic diagram of the biosynthesis of peptide transmitter/hormone and its effects on the target cell. The mRNA encoding the peptide precursor is transcribed in the nucleus and translated at the rough endoplasmic reticulum into a biological inactive precursor protein. The precursor protein is transported to the Golgi apparatus (Golgi) and packaged into the dense core secretory granules for further proteolytic processing and storage. Exocytosis of secretory granule releases the biological active peptides. When the peptide binds to its receptor (GPCR) in the target cell, it dissociates the Gα from Gβ and Gγ and activates the corresponding downstream effector proteins. In addition to the classic G proteins routes, GPCR activation can involve other signalling pathways such as β‐arrestin. The peptide–receptor interaction also initiates desensitisation through receptor endocytosis. The receptor could recycle back to the plasma membrane for another round of receptor activation.


Cawley NX, Wetsel WC, Murthy SR, et al. (2012) New roles of carboxypeptidase E in endocrine and neural function and cancer. Endocrine Reviews 33: 216–253.

Chen XY, Du YF and Chen L (2018) Neuropeptides exert neuroprotective effects in Alzheimer's disease. Frontiers in Molecular Neuroscience 11: 493.

El Filali Z, Hornshaw M, Smit AB and Li KW (2003) Retrograde labeling of single neurons in conjunction with MALDI high‐energy collision‐induced dissociation MS/MS analysis for peptide profiling and structural characterization. Analytical Chemistry 75: 2996–3000.

Godbole A, Lyga S, Lohse MJ and Calebiro D (2017) Internalized TSH receptors en route to the TGN induce local Gs‐protein signaling and gene transcription. Nature Communications 8: 443.

Guidolin D, Marcoli M, Tortorella C, Maura G and Agnati LF (2019) Receptor‐receptor interactions as a widespread phenomenon: novel targets for drug development? Front Endocrinol (Lausanne) 10: 53.

Hallberg M (2015) Neuropeptides: metabolism to bioactive fragments and the pharmacology of their receptors. Medicinal Research Reviews 35: 464–519.

Hokfelt T, Barde S, Xu ZD, et al. (2018) Neuropeptide and small transmitter coexistence: fundamental studies and relevance to mental illness. Front Neural Circuits 12: 106.

Johnson ZV and Young LJ (2017) Oxytocin and vasopressin neural networks: implications for social behavioral diversity and translational neuroscience. Neuroscience and Biobehavioral Reviews 76: 87–98.

Kastin AJ and Pan W (2010) Concepts for biologically active peptides. Current Pharmaceutical Design 16: 3390–3400.

van der Klaauw AA (2018) Neuropeptides in obesity and metabolic disease. Clinical Chemistry 64: 173–182.

Persoon CM, Moro A, Nassal JP, et al. (2018) Pool size estimations for dense‐core vesicles in mammalian CNS neurons. The EMBO Journal 37.

Seidah NG (2011) The proprotein convertases, 20 years later. Methods in Molecular Biology 768: 23–57.

Shintani Y, Hayata‐Takano A, Moriguchi K, et al. (2018) beta‐Arrestin1 and 2 differentially regulate PACAP‐induced PAC1 receptor signaling and trafficking. PLoS One 13: e0196946.

Smith SJ, Sumbul U, Graybuck L, et al. (2019) Single‐cell transcriptomics evidence for dense intracortical neuropeptide networks. elife. 8. pii: e47889. DOI: 10.7554/eLife.47889. (2019 Nov 11).

Yin P, Bousquet‐Moore D, Annangudi SP, et al. (2011) Probing the production of amidated peptides following genetic and dietary copper manipulations. PLoS One 6: e28679.

Further Reading

Van den Pol A (2012) Neuropeptide transmission in brain circuits. Neuron 76: 98–115.

Wang W, Qiao Y and Li Z (2018) New insights into modes of GPCR activation. Trends in Pharmacological Sciences 39: 367–386.

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Gonzalez‐Lozano, Miguel A, and Li, Ka Wan(May 2020) Peptide Neurotransmitters and Hormones. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000063.pub3]