Cellular and subcellular localization of neurokinin‐1 and neurokinin‐3 receptors in primate globus pallidus

Lévesque, Martin; Parent, Rémy; Parent, André

doi:10.1111/j.1460-9568.2006.04800.x

Cited by 16 publications

(10 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In SON and PVN, immunoreactivity for NK3-R observed with either confocal or electron microscopy has a clustered appearance in the neuronal nuclei (Howe et al, 2004; Haley and Flynn, 2006; Jensen et al, 2008). The nuclear immunoreactivity for NK3-R reported in globus pallidus and VTA has a similar clustered appearance (Levesque et al, 2006; Lessard et al, 2009). This clustered appearance is consistent with localization of NK3-R to nuclear suborganelles some of which are rich in histones (Handwerger and Gall, 2006; Misteli, 2007).…”

Section: Discussionmentioning

confidence: 61%

“…Altered NK3-R expression occurs in a strain of hamsters with dystonia (Friedman et al, 2002), and a NK3-R antagonist reduces blood pressure in spontaneously hypertensive rats (Lessard et al, 2003). Nuclear NK3-R-IR has recently been shown ultrastructurally in globus pallidus and VTA neurons (Levesque et al, 2006; Lessard et al, 2009). In the current studies, NK3-R was detected in nuclear fractions from all brain areas examined.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of nuclear neurokinin 3 receptor expression in rat brain

Sladek¹,

Stevens²,

Levinson³

et al. 2011

Neuroscience

View full text Add to dashboard Cite

Ligand-induced translocation of the G-protein-coupled receptor, neurokinin 3 (NK3-R), to the nucleus of hypothalamic neurons was reported using antibodies (ABs) raised against the C-terminal region of NK3-R. The current work was undertaken to substantiate the ability of NK3-R to enter the nucleus and identify which portion of the NK3-R molecule enters the nucleus. ABs directed at epitopes in the N-terminal and second extracellular loop of the rat NK3-R molecule were used to evaluate western blots of whole tissue homogenates and nuclear fractions from multiple brain areas. Specificity of the protein bands recognized by these ABs was demonstrated using CHO cells transfected with rat or human NK3-R. Both ABs prominently recognized a diffuse protein band of ~56–65kD (56kD=predicted size) and distinct ~70kD and 95kD proteins in homogenates of multiple brain areas. The ~95kD protein recognized by the extracellular loop AB was enriched in nuclear fractions. Recognition of these proteins by ABs directed at different regions of the NK3-R supports their identification as NK3-R. The size differences reflect variable glycosylation and possibly linkage to different cytosolic and nuclear proteins. Recognition of protein bands by both ABs in nuclear fractions is consistent with the full-length NK3-R entering the nucleus. Hypotension increased the density of the ~95kD band in nuclear fractions from the supraoptic nucleus indicating activity-induced nuclear translocation. Since NK3-R is widely distributed in the CNS, the presence of NK3-R in nuclei from multiple brain regions suggests that it may broadly influence CNS gene expression in a ligand-dependent manner.

show abstract

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Characterization of nuclear neurokinin 3 receptor expression in rat brain

Sladek¹,

Stevens²,

Levinson³

et al. 2011

Neuroscience

View full text Add to dashboard Cite

show abstract

“…Although the present focus is on the PVN, the same may apply to multiple other brain regions that express NK3R. Indeed, NK3R is detected within the nuclei of neurons in the globus pallidus and ventral tegmental area (40,41). Additional techniques were not used to identify whether nuclear NK3R in these brain areas associated with transcriptionally active chromatin, but the presence of the NK3R in nuclei of neurons in a variety of brain regions suggests that NK3R may affect gene activation under multiple conditions.…”

Section: Perspectives and Significancementioning

confidence: 88%

“…For example, under basal conditions, NK3R is found within the nucleus of neurons in the ventral tegmental area of rat (VTA) (40) and globus pallidus of squirrel monkeys (41). Limited NK3R is found in nuclei of SON neurons under basal conditions, but nuclear NK3R increases significantly in response to hypotension (26).…”

Section: Discussionmentioning

confidence: 99%

Neurokinin 3 receptor forms a complex with acetylated histone H3 and H4 in hypothalamic neurons following hyperosmotic challenge

Flynn

Jensen

Thakar³

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

The neurokinin 3 receptor (NK3R) is a G protein-coupled receptor that is expressed in brain and is highly expressed by magnocellular vasopressinergic neurons in both the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus. Hyperosmolarity causes a ligand-mediated internalization of NK3Rs to the cytoplasm and to the nuclei of vasopressinergic PVN neurons. This receptor activation-dependent pathway is presumed to be a means to directly transmit synaptic signals from the cell membrane to the nucleus. The present study evaluated in vivo the subnuclear domains that associate with NK3R. Rats were administered 2 M NaCl (intragastric) or no intragastric load, and 40 min later, the PVN was dissected and nuclei were isolated. Using double-immuno-transmission electron microscopy (TEM), we show that, compared with controls, hyperosmolarity causes a significant increase in NK3R Immunogold beads in the nucleus of PVN neurons. Furthermore, NK3R spatially colocalized with histone H4 and with highly acetylated H4 in nuclei isolated from the PVN of rats administered 2 M NaCl, but not in nuclei from control rats. Next, coimmunoprecipitation experiments showed that acetylated H4, as well as acetylated H3, were pulled down with NK3R in the PVN nuclear enriched fraction from rats treated with 2 M NaCl, but not from control rats. In response to hyperosmolarity, NK3R is transported to the nucleus of PVN neurons and associates with transcriptionally active chromatin, where it may influence the transcription of genes.

show abstract

“…Much evidence indicated the expression of neurokinin‐1 receptor in globus pallidus (Mantyh et al ., 1984; Mounir & Parent, 2002; Levesque et al ., 2006). It has been reported that substance P‐positive fibers from the striatum are closely apposed to pallidal neurons that express neurokinin‐1 receptors (Mounir & Parent, 2002; Levesque et al ., 2003).…”

Section: Introductionmentioning

confidence: 99%

Substance P excites globus pallidus neurons in vivo

Cui¹,

Yung²,

Xue³

et al. 2007

Eur J of Neuroscience

View full text Add to dashboard Cite

Substance P is a member of the neurokinin family. Previous studies have reported the existence of substance P and its high-affinity receptor, neurokinin-1 receptor, in globus pallidus. Employing in vivo extracellular recording combined with behavioural tests, the effects of substance P in globus pallidus of rats were studied. Micropressure ejection of the selective neurokinin-1 receptor agonist [Sar9,Met(O2)11] substance P increased the spontaneous firing rate of pallidal neurons in a concentration-dependent manner, with increases of 27.3% at 0.01, 33.4% at 0.03, 45.5% at 0.1, 38.4% at 0.3 and 36.4% at 1.0 mm. The selective neurokinin-1 receptor antagonist SR140333B prevented the excitatory effects induced by [Sar9,Met(O2)11] substance P. In behaving rats, we observed the postural effects of neurokinin-1 receptor activation in the globus pallidus. Consistent with electrophysiological results, unilateral microinjection of [Sar9,Met(O2)11] substance P (0.1 mm) led to a SR140333B-sensitive contralateral deflection in the presence of systemic haloperidol administration. Combining electrophysiological and behavioural findings, we concluded that substance P produces excitatory effects on globus pallidus neurons via neurokinin-1 receptors.

show abstract

Cellular and subcellular localization of neurokinin‐1 and neurokinin‐3 receptors in primate globus pallidus

Cited by 16 publications

References 55 publications

Characterization of nuclear neurokinin 3 receptor expression in rat brain

Characterization of nuclear neurokinin 3 receptor expression in rat brain

Neurokinin 3 receptor forms a complex with acetylated histone H3 and H4 in hypothalamic neurons following hyperosmotic challenge

Substance P excites globus pallidus neurons in vivo

Contact Info

Product

Resources

About