Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea

Drescher, Marian J.; Drescher, Dennis G.; Khan, Khalid M.; Hatfield, James S.; Ramakrishnan, Neeliyath A.; Abu-Hamdan, Maher; Lemonnier, Lori A.

doi:10.1016/j.neuroscience.2006.05.065

Cited by 28 publications

(34 citation statements)

References 65 publications

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“…The morphology of the inner ear showed no differences between the homozygous PACAP-defi cient and WT mice. Our research group found PAC1-R immunopositivity in both inner and outer hair cells, outer phalangeal cells (Deiters' cells), and pillar cells in accordance with the previous results of Kawano et al [ 3 ], AbuHamdan et al [ 1 ] and Drescher et al [ 2 ]. The localization of PAC1-R immunoreactivity did not show any differences between homozygous PACAP-defi cient and WT mice, but in PACAP-defi cient mice the hair cells and outer phalangeal cells showed lower intensity of PAC1-R immunoreactivity compared to WT mice.…”

Section: Pacap and Pac1-r In The Cochleasupporting

confidence: 93%

“…Drescher et al [ 2 ] examined the localization of PACAP, PAC1-R, and several afferent and efferent neuronal markers [choline acetyltransferase (ChAT), gluta-mate receptor 2/3 (GluR2/3), dopamine β-hydroxylase (DBH)] with immunohistochemistry in the cochlea of 2-month-old ACI Black Agouti rats. Their aim was to show the localization of PACAP and PAC1-R in the organ of Corti (Figs.…”

Section: Pacap and Pac1-r In The Cochleamentioning

confidence: 99%

“…Dopamine acts as a protective neurotransmitter in case of excitotoxicity for type I afferents [ 20 , 21 ] and PACAP is able to upregulate dopaminergic functions [ 22 ]. Drescher et al [ 2 ] showed more evidence for the previous fi ndings of Spoendlin [ 23 ], that adrenergic efferent innervation is also present in different sites of the organ of Corti, such as supranuclear sites of inner and outer hair cells, and Deiters' and Hensen's cell regions. PACAP is associated with adrenergic nerve terminals [ 24 ] and takes part in the modifi cation of adrenergic functions [ 25 ].…”

Section: Pacap and Pac1-r In The Cochleamentioning

confidence: 99%

“…Morio et al [ 29 ] showed that in neuronal cells PACAP suppressed glutamate-induced cell death. Drescher et al [ 2 ] demonstrated the presence of PAC1-R in cell bodies and dendrites of type I afferent cells in the spiral ganglion. It also showed colocalization with GluR2/3 under the outer hair cells in the organ of Corti suggesting that PACAP interacts directly with glutamatemediated signal transduction in the auditory system.…”

Section: Pacap and Pac1-r In The Cochleamentioning

confidence: 99%

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Pituitary Adenylate Cyclase-Activating Polypeptide in the Auditory System

Fülöp

Reglődi

Németh

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with well-known neurotrophic, neuroprotective, antioxidant, and antiapoptotic effects. It also exerts protective effects in sensory organs, such as visual and olfactory system. In this review we present data regarding the localization and effects of PACAP in the auditory system. PACAP and its specifi c receptor (PAC1-R) are present in the organ of Corti in hair cells, supporting cells, and different nerve fi bers. They are also present in the spiral ganglion showing co-localization with efferent fi bers of glutamatergic and adrenergic pathways, probably directly affecting the efferent signal transduction in the inner ear. PACAP and its specifi c receptor also occur in the stria vascularis suggesting a role in endolymph production; furthermore, they are present in central pathways of the auditory system such as the cochlear nuclei, superior olivary complex, inferior colliculus, and medial geniculate body. PAC1-receptor is also present in the inner ear in PACAP-defi cient mice, occurring at the same localization but with altered expression compared to wildtype mice. PACAP protects hair cells from H 2 O 2 -induced apoptosis in chicken inner ear cell cultures in vitro, and the lack of PACAP affects the Ca 2+ -binding protein expression in hair cells in PACAP-defi cient mice under control circumstances and after ototoxic drug treatment.

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Section: Pacap and Pac1-r In The Cochleasupporting

confidence: 93%

Section: Pacap and Pac1-r In The Cochleamentioning

confidence: 99%

Section: Pacap and Pac1-r In The Cochleamentioning

confidence: 99%

Section: Pacap and Pac1-r In The Cochleamentioning

confidence: 99%

See 2 more Smart Citations

Pituitary Adenylate Cyclase-Activating Polypeptide in the Auditory System

Fülöp

Reglődi

Németh

et al. 2016

Current Topics in Neurotoxicity

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“…The isolation of the rat cochlea for immunohistochemical analysis has been previously described (12). In brief, the bony cochleas from 2-month-old ACI Black Agouti rats were perfused from basal to apical coil with the fixative consisting of 4% paraformaldehyde, 0.1% glutaraldehyde in 0.1 M phosphate buffer, pH 7.4, at 4°C (13).…”

Section: Acquisition Of a Model Hair Cell Preparation From The Trout mentioning

confidence: 99%

Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3

Ramakrishnan

Drescher

Barretto

et al. 2009

Journal of Biological Chemistry

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The cytoplasmic amino terminus of HCN1, the primary full-length HCN isoform expressed in trout saccular hair cells, was found by yeast two-hybrid protocols to bind the cytoplasmic carboxyl-terminal domain of a protocadherin 15a-like protein. HCN1 was immunolocalized to discrete sites on saccular hair cell stereocilia, consistent with gradated distribution expected for tip link sites of protocadherin 15a. HCN1 message was also detected in cDNA libraries of rat cochlear inner and outer hair cells, and HCN1 protein was immunolocalized to cochlear hair cell stereocilia. As predicted by the trout hair cell model, the amino terminus of rat organ of Corti HCN1 was found by yeast two-hybrid analysis to bind the carboxyl terminus of protocadherin 15 CD3, a tip link protein implicated in mechanosensory transduction. Specific binding between HCN1 and protocadherin 15 CD3 was confirmed with pull-down assays and surface plasmon resonance analysis, both predicting dependence on Ca HCN12 is the primary full-length HCN isoform underlying I h (hyperpolarization-activated, cyclic nucleotide-gated, nonselective cation channel current) in a model hair cell preparation from the trout sacccule (1). cAMP-gated I h , possibly in addition to the mechanosensory-transduction current, sets the membrane potential for a subpopulation of saccular hair cells (2, 3). The membrane potential in the saccular hair cell subpopulation is sufficiently depolarized to activate voltage-gated calcium channels, permitting influx of calcium and secretion of hair cell transmitter (2). Given that saccular hair cells expressing I K1 in addition to I h are more hyperpolarized, not supporting activation of the voltage-gated calcium channels, we predicted that spontaneous release of transmitter from the subpopulation of hair cells would constitute hair cell-generated spontaneous activity for the saccule (1). However, little has been previously reported on the morphological localization of the HCN1 isoform in hair cells or possible links to structural proteins that mechanistically would localize HCN1 in hair cells (for preliminary report, see Ref. 4). In general, little is known about proteinprotein interactions for the HCN isoforms that would modulate I h and/or the associated instantaneous current (5).Protocadherin 15 is a proposed tip link protein involved in connecting shorter stereocilia to adjacent taller stereocilia in the stereociliary array of inner ear hair cells, facilitating the opening of the mechanosensory transduction channel in response to auditory and vestibular stimuli. The active tip link protein in Danio rerio is protocadherin 15a (6), characterized by splice variants in its carboxyl terminus. In the mammal, protocadherin 15 CD3 is hypothesized to be a tip link protein at insertion sites in the tips of the shorter stereocilia of the stereociliary array (7,8). EXPERIMENTAL PROCEDURES Acquisition of a Model Hair Cell Preparation from the Trout Saccule and an Organ of Corti Subfraction from theRat Cochlea-Hair cell layers were isolated from the t...

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Neurochemistry of Olivocochlear Neurons in the Hamster

Reuss

Disque-Kaiser

Antoniou-Lipfert

et al. 2009

The Anatomical Record

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The present study was conducted to characterize the superior olivary complex (SOC) of the lower brain stem in the pigmented Djungarian hamster Phodopus sungorus. Using Nissl-stained serial cryostat sections from fresh-frozen brains, we determined the borders of the SOC nuclei. We also identified olivocochlear (OC) neurons by retrograde neuronal tracing upon injection of Fluoro-Gold into the scala tympani. To evaluate the SOC as a putative source of neuronal nitric oxide synthase (nNOS), arginine-vasopressin (AVP), oxytocin (OT), vasoactive intestinal polypeptide (VIP), or pituitary adenylate cyclase-activating polypeptide (PACAP) that were all found in the cochlea, we conducted immunohistochemistry on sections exhibiting retrogradely labeled neurons. We did not observe AVP-, OT-, or VIP-immunoreactivity, neither in OC neurons nor in the SOC at all, revealing that cochlear AVP, OT, and VIP are of nonolivary origin. However, we found nNOS, the enzyme responsible for nitric oxide synthesis in neurons, and PACAP in neuronal perikarya of the SOC. Retrogradely labeled neurons of the lateral olivocochlear (LOC) system in the lateral superior olive did not contain PACAP and were only infrequently nNOS-immunoreactive. In contrast, some shell neurons and some of the medial OC (MOC) system exhibited immunofluorescence for either substance. Our data obtained from the dwarf hamster Phodopus sungorus confirm previous observations that a part of the LOC system is nitrergic. They further demonstrate that the medial olivocochlear system is partly nitrergic and use PACAP as neurotransmitter or modulator. Anat Rec, 292:461-471, 2009.

show abstract

Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea

Cited by 28 publications

References 65 publications

Pituitary Adenylate Cyclase-Activating Polypeptide in the Auditory System

Pituitary Adenylate Cyclase-Activating Polypeptide in the Auditory System

Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3

Neurochemistry of Olivocochlear Neurons in the Hamster

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