Differential localization of3H-[Pro9]SP binding sites in the guinea pig and rat brain

doi:10.1016/0006-8993(94)91555-5

Brain Research

Volume 633, Issues 1–2, 7 January 1994, Pages 317-325

https://doi.org/10.1016/0006-8993(94)91555-5 Get rights and content

Abstract

Due to the existence of differences in the pharmacological properties of tachykinin NK-1 receptors in the rat and the guinea pig, the autoradiographic distribution of NK-1 binding sites was compared in the brain of the two species using the selective NK-1 ligand³H-[Pro⁹]SP. If a good similarity in the distribution of NK-1 binding sites could be seen in basal ganglia, a relative absence of correlation was observed between the estimated optical densities in other brain structures of the two species. For instance, the interpeduncular nucleus, the lateral habenular nucleus and the deep layers of the cerebral cortex were labeled in the guinea pig but not in the rat while the reverse was observed for the columns of the vermis lobules 9–10, the dorsal raphe nucleus, the medial habenular nucleus, the superficial cortical layers and the dorsal hippocampus. Furthermore, the high similarity found in the localization of¹²⁵I-BHSP (a non selective ligand) and³H-[Pro⁹]SP binding sites, does not suggest the existence of NK-1 binding site subtypes in the guinea pig brain.

References (45)

AraiH. et al.
Regional distribution of neuropeptide K and other tachykinins (neurokinin A, neurokinin B and substance P) in rat central nervous system
Brain Res.
(1986)
ChassaingG. et al.
Homocysteine thiolactone as precursor of methionine amide: application to the modification of peptides of the tachykinin family
Tetrahedron lett.
(1985)
DamT.-V. et al.
Autoradiographic distribution of brain neurokinin-1/substance P receptors using a highly selective ligand [³H]-[Sar⁹, Met(O₂)¹¹] -substance P
Brain Res.
(1990)
DamT.-V. et al.
Pharmacological characterization and autoradiographic localization of substance P receptors in guinea pig brain
Peptides
(1986)
DietlM.M. et al.
Autoradiographic analysis of the distribution of vasoactive intestinal peptide binding sites in the vertebrate central nervous system: a phylogenetic study
Brain Res.
(1990)
DietlM.M. et al.
Phylogeny of tachykinin receptor localization in the vertebrate central nervous system: apparent absence of neurokinin-2 and neurokinin-3 binding sites in the human brain
Brain Res.
(1991)
FongT.M. et al.
Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580
J. Biol. Chem.
(1992)
GallagherA.W. et al.
Distribution of substance P-like immunoreactivity in guinea pig central nervous system
Brain Res. Bull.
(1992)
GitterB.D. et al.
Species differences in affinities of non-peptide antagonists for substance P receptors
Eur. J. Pharmacol.
(1991)
GorbulevV. et al.
Molecular cloning of substance P receptor cDNA from guinea-pig uterus
Biochim. Biophys. Acta
(1992)

LewR. et al.

Binding characteristics of [¹²⁵I]Bolton-Hunter [Sar⁹,Met(O₂)¹¹]substance P, a new selective radioligand for the NK1 receptor

Eur. J. Pharmacol.

(1990)

MantyhC.R. et al.

Diifferential localization of cholecystokinin-8 binding sites in the rat vs. the guinea pig brain

Eur. J. Pharmacol.

(1985)

PatacchiniR. et al.

Activity of peptide anad non-peptide antagonists at peripheral NK₁ receptors

Eur. J. Pharmacol.

(1992)

PerroneM.H. et al.

Binding of [³H]substance P to populative substance P receptors in rat brain membranes

Eur. J. Pharmacol.

(1983)

PetitetF. et al.

NK-1 tachykinin receptor in rat and guinea pig brains: pharmacological and autoradiographical evidence for a species difference

Peptides

(1993)

QuirionR. et al.

Comparative pharmcological properties and autoradiographic distribution of [³H]ethylketocyclazocine binding sites in rat and guinea pig brain

Life Sci.

(1983)

SachaisB.S. et al.

Molecular basis for the species selectivity of the substance P antagonist CP-96,345

J. Biol. Chem.

(1993)

SaffroyM. et al.

Localization of tachykinin binding sites (NK₁, NK₂, NK₃ ligands) in the rat brain

Peptides

(1988)

ShultsC.W. et al.

Autoradiographic localization of substance P receptors using¹²⁵I substance P

Peptides

(1982)

TakedaY. et al.

Molecular cloning, structural characterization and functional expression of the human substance P receptor

Biochem. Biophys. Res. Commun

(1991)

TorrensY. et al.

Tachykinin receptors: binding and cellular activity assays

Methods Neurosci.

(1991)

TousignantC. et al.

Characterization of NK-1 receptors in guinea pig and rat brain membranes with NK-1 peptides and non-peptides antagonist

Brain Research

(1992)

Cited by (18)

The role of lateral habenula-dorsal raphe nucleus circuits in higher brain functions and psychiatric illness
2015, Behavioural Brain Research
Citation Excerpt :
Regardless of whether one or both Hb nuclei contribute to SP projections to the DRN, these have a major impact on DRN function. SP receptors are found on GABAergic and glutamatergic neurons in the DRN [36–38]. Treatment with SP antagonists increases the firing rates of serotonergic neurons in the DRN [39,40], and stimulation of the Hb inhibits DRN neuronal firing [16].
Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb–DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb–DRN system in regulation of higher brain functions and the possible role of disturbed LHb–DRN function in the pathogenesis of psychiatric disorders, especially depression.
Substance P receptor antagonist in lateral habenula improves rat depression-like behavior
2014, Brain Research Bulletin
Citation Excerpt :
However, this effect of SPAs is not seen in the in vitro electrophysiological studies, suggesting that effect of SPAs is mediated indirectly from outside the DRN (Conley et al., 2002). In line with this, immunohistochemical studies have shown that SP receptors are sparingly expressed in DRN of guinea pigs (Saffroy et al., 1994) and while they are expressed in mice and rat DRN, they are found in GABAergic and glutamatergic neurons but not in 5-HT neurons (Santarelli et al., 2001; Froger et al., 2001; Ma and Bleasdale, 2002; Commons and Valentino, 2002; Liu et al., 2002). Lateral habenula (LHb) is a major relay station between forebrain and brain stem, and it is involved in the regulation of many physiological functions (Cohen and Melzack, 1993; Zhao and Rusak, 2005; Matsumoto and Hikosaka, 2007; Klemm, 2004; Bianco and Wilson, 2009; Hikosaka et al., 2008; Lecourtier and Kelly, 2007; Shen et al., 2012), especially those related to stress and emotional response (Lee and Huang, 1988; Ranft et al., 2010).
Substance P (SP) levels are closely related with the pathogenesis of depression. Recent work has focused on antidepressive effect of substance P receptor antagonist (SPA), however, its action site and mechanism remain largely unresolved. Our previous results showed that the lateral habenula (LHb) plays a key role in the pathogenesis of depression. The current study investigated the effects of SPA microinjected into LHb on the behavioral responses of two rat models that exhibit depression-like behavior. To produce adult rats that exhibit depression-like behavior, rats were either exposed to chronic mild stress (CMS), or chronically administered clomipramine (CLI), a tricyclic antidepressant, during the neonatal state of life. The forced-swimming test (FST) was used to evaluate behavioral responses. Furthermore, we measured serotonin (5-HT) levels in dorsal raphe nucleus (DRN) using microdialysis. The FST showed a decreased immobility time and an increased climbing time after SPA injection into the LHb of depression-like behavior rats. In addition, 5-HT levels in DRN increased after SPA was microinjected into LHb of the rats that exhibited depression-like behavior. This study demonstrates that LHb mediates antidepressive effect of SPA by increasing 5-HT levels in the DRN, suggesting that the LHb may be a potential target of antidepressant.
Neurokinin-1 receptor deletion modulates behavioural and neurochemical alterations in an animal model of depression
2012, Behavioural Brain Research
Citation Excerpt :
In addition to the regulation of serotonergic neurotransmission, the substance P/NK1 receptor system modulates noradrenergic functioning. NK1 receptors are highly expressed on noradrenergic neurons within the locus coeruleus [19,30], antagonism of which has been reported to increase neuronal burst firing [31,32] and noradrenergic release in the terminal field [33,34]. In addition, NK1−/− mice exhibit desensitisation of somatodendritic α2a-adrenoceptors which account in part for the enhanced extracellular noradrenaline in the frontal cortex [35].
The substance P/NK1 receptor system plays an important role in the regulation of stress and emotional responding and as such had been implicated in the pathophysiology of anxiety and depression. The present study investigated whether alterations in the substance P/NK1 receptor system in brain areas which regulate emotional responding accompany the depressive behavioural phenotype observed in the olfactory bulbectomised (OB) mouse. The effect of NK1 receptor deletion on behavioural responding and monoamine levels in discrete brain regions of the OB model, were also examined. Substance P levels in the frontal cortex and NK1 receptor expression in the amygdala and hippocampus were enhanced following olfactory bulbectomy. Although NK1 receptor knockout (NK1−/−) mice did not exhibit altered behavioural responding in the open field test, noradrenaline levels were enhanced in the frontal cortex, amygdala and hippocampus, as were serotonin levels in the frontal cortex. Locomotor activity and exploratory behaviour were enhanced in wild type OB mice, indicative of a depressive-like phenotype, an effect attenuated in NK1−/− mice. Bulbectomy induced a decrease in noradrenaline and 5-HIAA in the frontal cortex and an increase in serotonin in the amygdala, effects attenuated in OB NK1−/− mice. The present studies indicate that alterations in substance P/NK1 receptor system underlie, at least in part, the behavioural and monoaminergic changes in this animal model of depression.
A 25 year adventure in the field of tachykinins
2004, Peptides
Several aspects of our 25 year adventure in the field of tachykinins will be successively described. They concern: substance P (SP) synthesis and release in the basal ganglia, the identification and pharmacological characterization of central tachykinin NK₁, NK₂ and NK₃ binding sites and their topographical distribution, the description of some new biological tests for corresponding receptors, the identification of tachykinin NK₁ receptor subtypes or conformers sensitive to all endogenous tachykinins (substance P, neurokinin A (NKA), neurokinin B (NKB), neuropeptide γ (NPγ) and neuropeptide K (NPK)) and finally, the functional involvement of these receptors and their subtypes in tachykinin-induced regulations of dopamine and acetylcholine release in the striatum.
Subtypes of substance P receptor immunoreactive interneurons in the rat basolateral amygdala
2003, Brain Research
Citation Excerpt :
This apparent discrepancy with our results might simply be due to species differences in the expression pattern for substance P receptors. Indeed, there is evidence for major differences between these two species with respect to the density and localization of SPR expression in several brain regions [65]. The immunocytochemical data presented here also demonstrate significant differences in the expression pattern of the SPR in different brain regions.
Local injections of the neurotoxin SP-saporin into the basolateral amygdala (BLA) are reported to specifically lesion substance P receptor immunoreactive (SPR-IR) interneurons, and to reduce anxiety related behavior. Hence, this technique might provide a means to study how defined interneuron populations regulate neuronal activity in the BLA. However, what interneuron subgroups in the BLA might be targeted by SP-saporin lesions has not been established. This study has used dual-labeling immunofluorescence in the rat BLA to examine SPR-IR neurons for their colocalization with the calcium-binding proteins; calbindin-D28k (CB), parvalbumin (PV), and calretinin (CR); and the neuropeptides somatostatin (SOM) and neuropeptide Y (NPY). We found that all NPY-IR neurons and 45% of SOM-IR interneurons expressed SPR-IR, and that 50% and 51% of the SPR-IR interneuron population expressed NPY- and SOM-IR, respectively. Previous studies have reported that approximately a third of SOM-IR interneurons also express NPY, which suggests a large degree of overlap between the NPY, SOM and SPR expressing neurons in the BLA. We also found that the majority of SPR-IR cells were CB-IR (62%), but that these interneurons represented only 2.8% of the total CB-IR population. Moreover, SPR-IR interneurons did not express either PV-or CR- IR. Hence, SP-saporin lesions would ablate all interneurons in the BLA that contain NPY, but leave the majority of the CB-IR cells intact, and have no effect on the CR- and PV-IR populations. Consequently, these results support the use of SP-saporin lesions as a useful technique to study the role of NPY-IR interneurons in the BLA.
Local immune regulation in the central nervous system by substance P vs. glutamate
2001, Journal of Neuroimmunology
The response of parenchymal microglia to interferon-gamma (IFN-γ) varies across the brain. To ask if local neurochemicals contribute to site-specific control, the influence of substance P (SP) and glutamate was evaluated in brainstem vs. hippocampus. In brainstem, stereotaxic injection of SP increased class II MHC upregulation by IFN-γ, while a SP receptor antagonist (Spantide I) prevented it. In hippocampus, where the baseline response to IFN-γ was lower, SP was ineffective, but blocking glutamate enhanced the response in a proportion of rats. Attempts to understand and control immune activity in the CNS should take the local neurochemical environment into account.

View all citing articles on Scopus

View full text

Research reportDifferential localization of3H-[Pro9]SP binding sites in the guinea pig and rat brain

Abstract

Brain Res.

Tetrahedron lett.

Brain Res.

Peptides

Brain Res.

Brain Res.

J. Biol. Chem.

Brain Res. Bull.

Eur. J. Pharmacol.

Biochim. Biophys. Acta

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Peptides

Life Sci.

J. Biol. Chem.

Peptides

Peptides

Biochem. Biophys. Res. Commun

Methods Neurosci.

Brain Research

Research report
Differential localization of³H-[Pro⁹]SP binding sites in the guinea pig and rat brain