Atrial Natriuretic Peptide Improves Neurite Outgrowth from Spiral Ganglion Neurons In Vitro through a cGMP-Dependent Manner

The spiral ganglion neurons (SGNs) are the primary afferent neurons in the spiral ganglion (SG), while their degeneration or loss would cause sensorineural hearing loss. As a cardiac-derived hormone, atrial natriuretic peptide (ANP) plays a critical role in cardiovascular homeostasis through binding to its functional receptors (NPR-A and NPR-C). ANP and its receptors are widely expressed in the mammalian nervous system where they could be implicated in the regulation of multiple neural functions. Although previous studies have provided direct evidence for the presence of ANP and its functional receptors in the inner ear, their presence within the cochlear SG and their regulatory roles during auditory neurotransmission and development remain largely unknown. Based on our previous findings, we investigated the expression patterns of ANP and its receptors in the cochlear SG and dissociated SGNs and determined the influence of ANP on neurite outgrowth in vitro by using organotypic SG explants and dissociated SGN cultures from postnatal rats. We have demonstrated that ANP and its receptors are expressed in neurons within the cochlear SG of postnatal rat, while ANP may promote neurite outgrowth of SGNs via the NPR-A/cGMP/PKG pathway in a dose-dependent manner. These results indicate that ANP would play a role in normal neuritogenesis of SGN during cochlear development and represents a potential therapeutic candidate to enhance regeneration and regrowth of SGN neurites.

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Atrial Natriuretic Peptide Promotes Neurite Outgrowth and Survival of Cochlear Spiral Ganglion Neurons in vitro Through NPR-A/cGMP/PKG Signaling

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.681421 ◽

2021 ◽

Vol 9 ◽

Author(s):

Fei Sun ◽

Ke Zhou ◽

Ke-yong Tian ◽

Xin-yu Zhang ◽

Wei Liu ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Neurite Outgrowth ◽

Natriuretic Peptide ◽

Neuronal Survival ◽

Spiral Ganglion ◽

Bioactive Molecules ◽

Spiral Ganglion Neurons ◽

Ganglion Neurons ◽

Atrial Natriuretic

Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3’,5’-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptor by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions. Despite former literatures and our reports indicating the existence of ANP and its receptors within the inner ear, particularly in the spiral ganglion, their potential regulatory mechanisms underlying functional properties of auditory neurons are still incompletely understood. Our recently published investigation revealed that ANP could promote the neurite outgrowth of SGNs by activating NPR-A/cGMP/PKG cascade in a dose-dependent manner. In the present research, the influence of ANP and its receptor-mediated downstream signaling pathways on neurite outgrowth, neurite attraction, and neuronal survival of SGNs in vitro was evaluated by employing cultures of organotypic explant and dissociated neuron from postnatal rats. Our data indicated that ANP could support and attract neurite outgrowth of SGNs and possess a high capacity to improve neuronal survival of SGNs against glutamate-induced excitotoxicity by triggering the NPR-A/cGMP/PKG pathway. The neuroregenerative and neuroprotective effects of ANP/NPRA/cGMP/PKG-dependent signaling on SGNs would represent an attractive therapeutic candidate for hearing impairment.

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Expression and localization of atrial natriuretic peptide and its receptors in rat spiral ganglion neurons

Brain Research Bulletin ◽

10.1016/j.brainresbull.2013.04.001 ◽

2013 ◽

Vol 95 ◽

pp. 28-32 ◽

Cited By ~ 4

Author(s):

Fei Sun ◽

Ke Zhou ◽

Shu-juan Wang ◽

Peng-fei Liang ◽

Yong-xiang Wu ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Ganglion Neurons ◽

Atrial Natriuretic

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Endogenous atrial natriuretic peptide inhibits endothelin-1 secretion in dogs with severe congestive heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.5.h1819 ◽

1996 ◽

Vol 270 (5) ◽

pp. H1819-H1824 ◽

Cited By ~ 8

Author(s):

A. Wada ◽

T. Tsutamato ◽

Y. Maeda ◽

T. Kanamori ◽

Y. Matsuda ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Arterial Pressure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Severe Congestive Heart Failure ◽

Dependent Manner ◽

Endothelin 1 ◽

Atrial Natriuretic

Atrial natriuretic peptide (ANP) has been shown to counteract the response of endothelin-1 (ET-1), but whether endogenous ANP actually inhibits the systemic release of ET-1 in vivo has not yet been determined. We administered HS-142-1 (HS), a specific antagonist of the guanylate cyclase-coupled ANP receptor, to conscious dogs with severe congestive heart failure (CHF) produced by rapid right ventricular pacing (n = 5, for 22 days) at doses of 0.3, 1.0, and 3.0 mg/kg at 30-minutes intervals. In the present study, plasma ANP and ET-1 levels were significantly elevated in CHF(348 +/-58 and 4.54 +/- 0.60 pg/ml, respectively compared with those in control dogs (65 +/- 4, P < 0.01, 1.30 +/- 0.17 pg/ml, P < 0.001). HS inhibited plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels, a biological market of endogenous ANP activity, in a dose-dependent manner from 21.8 +/- 2.2 to 7.2 +/- 1.4 pmol/ml (P < 0.001), with concomitant significant increases in plasma ET-1 levels from 4.54 +/- 0.60 to 6.60 +/- 0.72 pg/ml (P < 0.05). There was a significant negative correlation between the decrease in plasma cGMP and the increment in plasma ET-1 (r = -0.64, P < 0.01). Despite these responses, mean arterial pressure and pulmonary arterial pressure did not change significantly. Plasma angiotensin II and arginine vasopressin levels, both of which have been reported to stimulate ET-1 secretion in vitro, also showed no significant changes. These results strongly suggest that endogenous ANP directly inhibits endogenous ET-1 secretion through a cGMP-mediated pathway in chronic severe CHF.

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Inhibition of the c-Jun N-Terminal Kinase Signaling Pathway Influences Neurite Outgrowth of Spiral Ganglion Neurons In Vitro

The Laryngoscope ◽

10.1097/00005537-200211000-00028 ◽

2002 ◽

Vol 112 (11) ◽

pp. 2057-2061 ◽

Cited By ~ 21

Author(s):

Daniel Bodmer ◽

Bertrand Gloddek ◽

Allen F. Ryan ◽

Jochen Huverstuhl ◽

Dominik Brors

Keyword(s):

Neurite Outgrowth ◽

Signaling Pathway ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Kinase Signaling ◽

Ganglion Neurons ◽

Kinase Signaling Pathway

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Atrial natriuretic peptide induces acrosomal exocytosis in bovine spermatozoa

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.2.e216 ◽

1995 ◽

Vol 269 (2) ◽

pp. E216-E221 ◽

Cited By ~ 2

Author(s):

N. Zamir ◽

D. Barkan ◽

N. Keynan ◽

Z. Naor ◽

H. Breitbart

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Guanylyl Cyclase ◽

Acrosome Reaction ◽

Soluble Form ◽

Dependent Manner ◽

Subsequent Formation ◽

Acrosomal Exocytosis ◽

Atrial Natriuretic

The induction of acrosomal exocytosis in capacitated bull spermatozoa by atrial natriuretic peptide (ANP) was studied in vitro. ANP markedly stimulated acrosomal exocytosis in a calcium-dependent manner. Typically, ANP exerts its action via activation of the ANP receptor (ANPR-A), a particulate guanylyl cyclase-linked receptor, and subsequent formation of guanosine 3',5'-cyclic monophosphate (cGMP). We found that the ANP-induced acrosome reaction was inhibited by the competitive ANPR-A receptor antagonist-anantin, indicating a receptor-mediated effect. We could mimic the effect of ANP on the acrosome reaction by using 8-bromo-cGMP, suggesting that cGMP may serve as a signal transducer mediating the acrosome reaction. Indeed, the ANP-induced acrosome reaction was associated with elevation of cGMP levels. cGMP can also be formed by activation of the soluble form of guanylyl cyclase. Sodium nitroprusside (SNP) stimulated cGMP accumulation and acrosome reaction of capacitated spermatozoa. Thus ANP and the nitric oxide-releasing compound SNP, via activation of guanylyl cyclase (the former activating the particulate and the latter activating the soluble form of the enzyme), may play a significant role in the induction of the acrosome reaction.

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