Neuropeptide W has Cell Phenotype‐Specific Effects on the Excitability of Different Subpopulations of Paraventricular Nucleus Neurones

Abstract

Administration of the neuropeptides NPW and NPB in rodents has been shown to influence the activity of a variety of autonomic and neuroendocrine systems. The paraventricular nucleus is a major autonomic and neuroendocrine integration site in the hypothalamus and neurons within this nucleus express the receptor for these ligands, neuropeptide B/W receptor 1 (NPBWR1). Therefore we used whole cell patch clamp recordings coupled with single cell RT-PCR to examine the effects of neuropeptide W-23 (NPW-23) on the excitability of identified paraventricular nucleus neurons. Oxytocin, vasopressin and thyrotropin releasing hormone neurons were all found to be responsive to 10 nM NPW-23, although both depolarizing and hyperpolarizing effects were observed in each of these cell groups. In contrast corticotropin releasing hormone cells were unaffected. Further subdivision of chemically phenotyped cell groups into magnocellular, neuroendocrine or pre-autonomic neurons, using their electrophysiological fingerprints, revealed that neurons projecting to medullary and spinal targets were predominantly inhibited by NPW-23 while those that projected to median eminence or neural lobe showed nearly equivalent numbers of depolarizing and hyperpolarizing cells. The demonstration of particular phenotypic populations of paraventricular nucleus neurons showing NPW-induced effects on excitability reinforces the importance of the NPB/NPW neuropeptide system as a regulator of autonomic function.

Neuropeptide W increases mean arterial pressure as a result of behavioral arousal

“…Neuropeptide W (NPW) is produced in, and influences the membrane potential of, neurons in the PVN, an area of the brain that communicates extensively with preautonomic centers in the brain stem and spinal cord (9,17,18,19) and is important for the regulation of ingestive behaviors (5,19). Our laboratory previously reported the ability of exogenously applied NPW to significantly increase both food and water intake during the light phase (1).…”

Cloning and distribution of neuropeptide W and its receptors in pigs

“…Murao, 2005). Another study demonstrated that NPW23 influences the PVN neurons that synthesize oxytocin, vasopressin, and thyrotropinreleasing hormone (Price et al, 2009). These findings suggest that NPW neurons in the PVN are involved in neuroendocrine and autonomic regulation (Sakurai, 2013).…”

Analgesic Neuropeptide W Suppresses Seizures in the Brain Revealed by Rational Repositioning and Peptide Engineering

“…Of particular interest, Zaratin and coworkers reported increased expression of NPBW 1 receptor subtypes in myelin-forming Schwann cells in animal models of acute inflammatory and traumainduced neuropathic pain, suggesting a central role for this peptide as an analgesic (16). Price et al showed that direct injection of NPW-23 into the hypothalamus influenced the excitability of specific groups of neurons in rats (17,18). In short, NPW has been shown to be a multifunctional endogenous ligand for NPBW 1 (19).…”

“…It has been previously reported that activation of NPBW 1 modulates hyperexcitability of neurons in the CNS (25). Price and co-workers previously reported that application of NPW to neurons in the paraventricular nucleus (PVN) of the hypothalamus resulted in a large population of hyperpolarized neurons (57%) with smaller mixed populations of depolarized and unchanged neurons (18). We hypothesize that the observed anticonvulsant effects exerted by hNPW-23, and the modified NPW analogues, resulted from activation of the NPBW 1 receptor which may result in hyperpolarization of the cell membrane.…”

“…Design of BBB-permeable NPW analogues was based on previous structure-activity relationship (SAR) findings that the C-terminal fragment NPW [14][15][16][17][18][19][20][21][22][23] and the N-terminal tripeptide of NPW are important for its structural and functional properties (24). Furthermore, Kanesaka and co-workers constructed centrally truncated analogues of NPW in which nonessential amino acid residues were replaced by backbone spacer units (5-aminovaleric acid), resulting in potent and selective NPWB 1 agonists (12).…”