Neuroendocrine Regulatory Peptide

Definition
are derived from distinct regions of VGF, a neurosecretory protein that was originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. NERPs are novel hypothalamic peptides involved in the control of body fluid homeostasis by regulating vasopressin release1.

Related peptides
The two amidated peptides NERP 1 and 2, with monoisotopic masses of 2677.4 and 4062.2, were derived from distinct regions of the neurosecretory protein VGF; one is from human VGF-(281–306), and the other is from VGF-(310 –347) 2.

Discovery
Yamaguchi et al, analyzed peptides secreted from human medullary thyroid carcinoma TT cells that produce amidated peptides. They identified two novel amidated peptides and designated them as neuroendocrine regulatory peptide (NERP)-1 and NERP-22.

Structural Characteristics
Molecular masses of human NERP-1 and 2 were found to be 2677 Da and 4062 Da, respectively2. The amino acid length of human NERP-1 is 26, and that of rat NERP-1 is 25. Human and rat NERP-2 are both 38 amino acid peptides1. The processing and amidation of NERPs occur intracellularly before secretion, as is known with amidated bioactive peptides secreted by endocrine cells. Bioactivity of NERPs requires C-terminal amidation which is a post translational modification1.

Mode of Action
Vasopressin release is regulated by the electrical activity of vasopressin neurons, which are modulated by various neurotransmitters and neuromodulators. The major neural signals to vasopressin neurons are excitatory and inhibitory postsynaptic currents generated by presynaptic release of glutamate and ?-aminobutyric acid, respectively. Angiotensin-II (AII) and NaCl potentiate excitatory postsynaptic currents in vasopressin neurons, thereby stimulating vasopressin secretion. Although cell-surface receptors or target proteins of NERPs have not been identified yet, the actions of NERP to suppress AII- and NaCl-induced vasopressin release from the hypothalamus may suggest that they presynaptically inhibit the glutamatergic inputs or enhance GABAergic inputs to vasopressin neurons2.

Functions
NERPs are novel bioactive peptides involved in body fluid homeostasis; they appear to modulate the actions and secretions of other neuropeptides. NERPs participate in the hypothalamic control of plasma osmolarity balance. Both NERP-1 and NERP-2 are potent endogenous suppressors of vasopressin release. All these actions were observed with C-terminally amidated forms only2.

References
1.Toshinai K and Nakazato M (2009). Neuroendocrine regulatory peptide-1 and -2: Novel bioactive peptides processed from VGF. Cell. Mol. Life Sci., 66(11-12):1939-1945.
2.Yamaguchi H, Sasaki K, Satomi Y, Shimbara T, Kageyama H, Mondal MS, Toshinai K, Date Y, González LJ, Shioda S, Takao T, Nakazato M, Minamino N (2007). Peptidomic Identification and Biological Validation of Neuroendocrine Regulatory Peptide-1 and -2. J Biol Chem., 282(36):26354-26360.