Peptide Neurotransmitters and Hormones

Abstract

Neuropeptides are 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 the 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 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 co‐packaged in the dense core secretory granules.

  • Receptors for neuropeptides belong mainly to the family of G protein‐coupled receptor.

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

Figure 1.

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 (ER) into a biological inactive precursor protein. The precursor protein is transported to the Golgi apparatus (Golgi) and packaged into the dense core secretory granules (SG) 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. These events are depicted by the blue arrows. 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. These events are depicted by the yellow arrows.

Figure 2.

Structural organisation of proopiomelanocortin and its tissue‐specific processing in the pituitary gland. In the pituitary anterior lobe corticotrophs, PC1/3 is the predominant convertase and its action results in the release of intact ACTH and small amounts of β‐endorphin (β‐END), in addition to a number of other peptides. In the pituitary intermediate lobe, both PC2 and PC1/3 are expressed, resulting in the further processing of ACTH to α‐melanophore‐stimulating hormone with increased production of β‐END. R, Arg; K, Lys; sp, signal peptide; JP, joining peptide; LPH, lipotropic hormone; CLIP, corticotropin‐like intermediate lobe protein. Adapted from Zhou et al..

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References

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.

DeFea KA (2011) Beta‐arrestins as regulators of signal termination and transduction: how do they determine what to scaffold? Cellular Signalling 23: 621–629.

Dikeakos JD and Reudelhuber TL (2007) Sending proteins to dense core secretory granules: still a lot to sort out. Journal of Cell Biology 177: 191–196.

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.

Feinstein TN, Wehbi VL, Ardura JA et al. (2011) Retromer terminates the generation of cAMP by internalized PTH receptors. Nature Chemical Biology 7: 278–284.

Hashimoto S, Fumagalli G, Zanini A and Meldolesi J (1987) Sorting of three secretory proteins to distinct secretory granules in acidophilic cells of cow anterior pituitary. Journal of Cell Biology 105: 1579–1586.

Hook V, Funkelstein L, Lu D et al. (2008) Proteases for processing proneuropeptides into peptide neurotransmitters and hormones. Annual Review of Pharmacology and Toxicology 48: 393–423.

Jean‐Alphonse F and Hanyaloglu AC (2011) Regulation of GPCR signal networks via membrane trafficking. Molecular and Cellular Endocrinology 331: 205–214.

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

Knowles MK, Barg S, Wan L et al. (2010) Single secretory granules of live cells recruit syntaxin‐1 and synaptosomal associated protein 25 (SNAP‐25) in large copy numbers. Proceedings of the National Academy of Sciences of the USA 107: 20810–20815.

Li KW, Jimenez CR, Van Veelen PA and Geraerts WP (1994) Processing and targeting of a molluscan egg‐laying peptide prohormone as revealed by mass spectrometric peptide fingerprinting and peptide sequencing. Endocrinology 134: 1812–1819.

Ma G‐Q, Wang B, Wang H‐B, Wang Q and Bao L (2008) Short elements with charged amino acids form clusters to sort protachykinin into large dense‐core vesicles. Traffic (Copenhagen, Denmark) 9: 2165–2179.

Macdonald K and Macdonald TM (2010) The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harvard Review of Psychiatry 18: 1–21.

Oldham WM and Hamm HE (2008) Heterotrimeric G protein activation by G‐protein‐coupled receptors. Nature Reviews Molecular Cell Biology 9: 60–71.

Otero MJ, Iglesias T and Fuentes JA (1993) Hypoalgesic action of bestatin analogues that inhibit central aminopeptidases, but not neutral endopeptidase. Neuropeptides 25: 175–182.

Pal K, Swaminathan K, Xu HE and Pioszak AA (2010) Structural basis for hormone recognition by the Human CRFR2alpha G protein‐coupled receptor. Journal of Biological Chemistry 285: 40351–40361.

Reche I, Ruiz‐Gayo M and Fuentes JA (1998) Inhibition of opioid‐degrading enzymes potentiates delta9‐tetrahydrocannabinol‐induced antinociception in mice. Neuropharmacology 37: 215–222.

Reglodi D, Kiss P, Lubics A and Tamas A (2011) Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Current Pharmaceutical Design 17: 962–972.

Rehfeld JF and Bundgaard JR (2010) Cell‐specific precursor processing. Results and Problems in Cell Differentiation 50: 45–62.

Roques BP and Noble F (1995) Dual inhibitors of enkephalin‐degrading enzymes (neutral endopeptidase 24.11 and aminopeptidase N) as potential new medications in the management of pain and opioid addiction. NIDA Research Monograph 147: 104–145.

Rozenfeld R and Devi LA (2011) Exploring a role for heteromerization in GPCR signalling specificity. Biochemical Journal 433: 11–18.

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

Skidgel RA and Erdos EG (2004) Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow‐ups to early studies. Peptides 25: 521–525.

Smith NJ and Milligan G (2010) Allostery at G protein‐coupled receptor homo‐ and heteromers: uncharted pharmacological landscapes. Pharmacological Reviews 62: 701–725.

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.

Zhou A, Webb G, Zhu X and Steiner DF (1999) Proteolytic processing in the secretory pathway. Journal of Biological Chemistry 274: 20745–20748.

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Li, Ka Wan(Dec 2012) Peptide Neurotransmitters and Hormones. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000063.pub2]