Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat

Ding, Yu; Shigemoto, Ryuichi; Takada, Masahiko; Ohishi, Hitoshi; Nakanishi, Shigetada; Mizuno, Noboru

doi:10.1002/(sici)1096-9861(19960108)364:2<290::aid-cne8>3.0.co;2-0

Cited by 170 publications

(61 citation statements)

References 55 publications

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“…SP interacts with NK1 receptors, NKA with NK2 receptors and NKB with NK3 receptors (Rekling et al 2000). Our focus on NK1 receptors was based on extensive anatomical and electrophysiological evidence that: (i) of the three neurokinin receptors, NK1 receptors are predominantly expressed in spinal motoneurons (Dam et al 1990a(Dam et al ,b, 1993Yashpal et al 1990;Beresford et al 1992;Nakaya et al 1994;Ding et al 1996;Manaker & Zucchi, 1998); (ii) that the postsynaptic actions of SP are mimicked by NK1 agonists (Fisher et al 1994;Lepre et al 1996);and (iii) that the minor effects of NKA and NKB receptor stimulation are largely blocked by TTX, suggesting a presynaptic location (Matsuto et al 1984;Fisher et al 1994;Ptak et al 2000). Antagonism of NK1 receptors has variable effects on SP or NK1 agonistinduced depolarization in neonatal tissue.…”

Section: Discussionsupporting

confidence: 69%

“…This variable sensitivity of SP-induced currents in neonatal spinal MNs to NK1 receptor antagonists may reflect activation of a mixed population of receptors in neonates as expression of all subunits is developmentally regulated (Charlton & Helke, 1986;Quirion & Dam, 1986;Beresford et al 1992;Dam et al 1993). Immunohistochemical and binding studies indicate that neither NKB-immunoreactive fibres (Too & Maggio, 1991;Marksteiner et al 1992;Merchenthaler et al 1992), nor NK2 nor NK3 receptors are prominent in motor nuclei in the adult (Yashpal et al 1990;Dam et al 1993;Ding et al 1996;Shughrue et al 1996), but high levels of NK3 receptor binding sites are present in the ventral horn of neonates (Beresford et al 1992).…”

Section: Discussionmentioning

confidence: 99%

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Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro

Yasuda

Robinson

Selvaratnam

et al. 2001

The Journal of Physiology

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The effects of substance P (SP), acting at NK1 receptors, on the excitability and inspiratory activity of hypoglossal (XII) motoneurons (MNs) were investigated using rhythmically active medullary‐slice preparations from neonatal mice (postnatal day 0‐3). Local application of the NK1 agonist [SAR9,Met (O2)11]‐SP (SPNK1) produced a dose‐dependent, spantide‐ (a non‐specific NK receptor antagonist) and GR82334‐(an NK1 antagonist) sensitive increase in inspiratory burst amplitude recorded from XII nerves. Under current clamp, SPNK1 significantly depolarized XII MNs, potentiated repetitive firing responses to injected currents and produced a leftward shift in the firing frequency‐current relationships without affecting slope. Under voltage clamp, SPNK1 evoked an inward current and increased input resistance, but had no effect on inspiratory synaptic currents. SPNK1 currents persisted in the presence of TTX, were GR82334 sensitive, were reduced with hyperpolarization and reversed near the expected EK. Effects of the α1‐noradrenergic receptor agonist phenylephrine (PE) on repetitive firing behaviour were virtually identical to those of SPNK1. Moreover, SPNK1 currents were completely occluded by PE, suggesting that common intracellular pathways mediate the actions of NK1 and α1‐noradrenergic receptors. In spite of the similar actions of SPNK1 and PE on XII MN responses to somally injected current, α1‐noradrenergic receptor activation potentiated inspiratory synaptic currents and was more than twice as effective in potentiating XII nerve inspiratory burst amplitude. GR82334 reduced XII nerve inspiratory burst amplitude and generated a small outward current in XII MNs. These observations, together with the first immunohistochemical evidence in the newborn for SP immunopositive terminals in the vicinity of SPNK1‐sensitive inspiratory XII MNs, support the endogenous modulation of XII MN excitability by SP. In contrast to phrenic MNs (Ptak et al. 2000), blocking NMDA receptors with AP5 had no effect on the modulation of XII nerve activity by SPNK1. In conclusion, SPNK1 modulates XII motoneuron responses to inspiratory drive primarily through inhibition of a resting, postsynaptic K+ leak conductance. The results establish the functional significance of SP in controlling upper airway tone during early postnatal life and indicate differential modulation of motoneurons controlling airway and pump muscles by SP.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro

Yasuda

Robinson

Selvaratnam

et al. 2001

The Journal of Physiology

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“…Both, SP and NKB immunoreactive nerve fibers and terminals have been detected in the DRN (Cuello and Kanazawa 1978;Marksteiner et al 1992). In situ hybridization studies show that there are NK 1 receptor mRNA-positive neurons in the periaqueductal gray and DRN (Maeno et al 1993) and NK 3 receptor mRNApositive neurons in various raphe nuclei, including the DRN (Ding et al 1996;Mileusnic et al 1999). However, it has been reported recently that NK 1 receptors in the DRN are located on non-5-HT neurons rather than 5-HT neurons (Froger et al 2001).…”

mentioning

confidence: 64%

Neurokinins Activate Local Glutamatergic Inputs to Serotonergic Neurons of the Dorsal Raphe Nucleus

Liu

Ding

Aghajanian

2002

Neuropsychopharmacology

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“…NK3-Rs are widespread in the brain, including areas that are implicated in processes governing learning and memory such as the hippocampus, frontal cortex (FC), and medial septum (10,11). There is a close interaction between NK3-R and the cholinergic system.…”

Section: Senktide | In Vivo Microdialysismentioning

confidence: 99%

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

Silva

Lenz

Rotter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism. senktide | in vivo microdialysis H umans exhibit a decline in cognitive capacity with age, which may progressively lead to dementia (1). Age-dependent morphological and physiological changes within the cholinergic system of the brain have been described as a major mechanism underlying impairments of learning and memory (2, 3). Numerous studies in aged rats have revealed that a degeneration of cholinergic neurons in the basal forebrain is associated with learning and >memory deficits (4). Likewise, the consistent correlations found between cholinergic degeneration and cognitive impairments indicate a high correspondence between acetylcholinergic activity and the magnitude of cognitive decline (4-6). This relationship has also been shown in patients with Alzheimer's disease (7,8).The neuropeptide neurokinins (NKs) substance P, neurokinin A, neurokinin B (NK-B), neuropeptide K, neuropeptide γ, and hemokinin 1 bind to the three known NK-receptors (NK3-R) (NK1-, NK2-, and NK3-R) with different degrees of affinity, whereby NK-B is the preferred ligand to NK3-R (9). NK3-Rs are widespread in the brain, including areas that are implicated in processes governing learning and memory such as the hippocampus, frontal cortex (FC), and medial septum (10, 11). There is a close interaction between NK3-R and the cholinergic system. NK3-R are localized on cholinacetyltransferase-containing neurons in ...

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Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat

Cited by 170 publications

References 55 publications

Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro

Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro

Neurokinins Activate Local Glutamatergic Inputs to Serotonergic Neurons of the Dorsal Raphe Nucleus

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

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