Distribution and pharmacological characterization of primate NK-2 tachykinin receptor in the central nervous system of the rhesus monkey
Highlights
► NK-2 receptors cloned from the rhesus monkey brain showed similar pharmacological properties to those of human NK-2 receptors. ► Substantial expression levels of NK-2 mRNA were observed in the monkey brain, including areas pertinent to the emotional networks. ► Our data suggest that NK-2 receptors play important roles in the pathophysiology of psychiatric disorders.
Section snippets
Contributors
Takao Oishi participated in the dissection and subdivision of the rhesus monkey brains. Masatoshi Nagano participated in the study design, cloning and quantification of NK-2 receptor mRNA, establishment of the cell lines expressing tachykinin receptors, ligand binding experiments and the writing of the manuscript. Hidenori Suzuki participated in the study design and supervision, and in the writing of the manuscript. All the authors have approved the final version of the manuscript.
Conflict of interest statement
All authors declare that they have no conflicts of interest.
Acknowledgments
This study was supported by the Cooperation Research Program (Project Nos. 2009-B6 and 2010-B12) from the Primate Research Institute, Kyoto University, a Grant-in-Aid for Scientific Research (19590261 to H.S.) and a grant (S0801035 to H.S.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
References (37)
- et al.
Expression of tachykinin NK2 receptor mRNA in human brain
Neurosci. Lett.
(2001) - 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) - et al.
Isolation and characterisation of the human lung NK-2 receptor gene using rapid amplification of cDNA ends
Biochem. Biophys. Res. Commun.
(1991) - et al.
Neuropeptides in cerebral cortex of Macaque monkey (Macaca fuscata fuscata): regional distribution and ontogeny
Brain Res.
(1986) - et al.
Changed concentrations of tachykinins and neuropeptide Y in brain of a rat model of depression: lithium treatment normalizes tachykinins
Neuropsychopharmacology
(2001) - et al.
Brainstem peptidergic neurons projecting to the medial and lateral thalamus and zona incerta in the rat
Brain Res.
(1993) The mammalian tachykinin receptors
Gen. Pharmacol.
(1995)- et al.
The autoradiographic localization of substance P receptors in the rat and bovine spinal cord and the rat and cat spinal trigeminal nucleus pars caudalis and the effects of neonatal capsaicin
Brain Res.
(1985) - et al.
Behavioral effects of saredutant, a tachykinin NK2 receptor antagonist, in experimental models of mood disorders under basal and stress-related conditions
Pharmacol. Biochem. Behav.
(2008) - et al.
Development of GAP-43 mRNA in the macaque cerebral cortex
Dev. Brain Res.
(1998)
Saredutant, an NK2 receptor antagonist, has both antidepressant-like effects and synergizes with desipramine in an animal model of depression
Pharmacol. Biochem. Behav.
mRNA expression of tachykinins and tachykinin receptors in different human tissues
Eur. J. Pharmacol.
Autoradiographic distribution of tachykinin NK2 binding sites in the rat brain: comparison with NK1 and NK3 binding sites
Neuroscience
Effects of central administration of tachykinin receptor agonists and antagonists on plus-maze behavior in mice
Eur. J. Pharmacol.
Pharmacological characterization of cloned human NK-2 (neurokinin A) receptor expressed in a baculovirus/Sf-21 insect cell system
Mol. Pharmacol.
Subtype- and species-selectivity of a tachykinin receptor antagonist, FK888, for cloned rat and human tachykinin receptors
Eur. J. Pharmacol.
Different subtypes of tachykinin NK1 receptor binding sites are present in the rat brain
J. Neurochem.
Neuroanatomy of anxiety
Curr. Top. Behav. Neurosci.
Cited by (5)
Mapping the binding pocket of a novel, high-affinity, slow dissociating tachykinin NK<inf>3</inf> receptor antagonist: Biochemical and electrophysiological characterization
2014, NeuropharmacologyCitation Excerpt :Moreover, recent findings have demonstrated that four out of nine multiplex families affected by hypogonadotropic hypogonadism carry loss-of-function mutations in NKB or the hNK3 receptor, hence indicating that NKB/NK3 signaling also plays a key role in the hypothalamic regulation of reproduction in humans (Silveira et al., 2010; Topaloglu et al., 2009). Although NK2 receptors are mainly found in the peripheral nervous system on end-organs, such as airway, bladder, and gastrointestinal (GI) tract smooth muscles (Evangelista et al., 2003), highly localized expression of NK2 receptors were also detected in brain areas related to emotional networks, anxiety and depression including PFC (infralimbic cortex), cingulate cortex, hippocampus, nucleus accumbens, amygdala, mediodorsal thalamus, and lateral septum (Bensaid et al., 2001; Nagano et al., 2011; Saffroy et al., 2003). Preclinical investigations with an NK2 antagonist, saredutant (SR48968) have shown anxiolytic and antidepressant-like effects in various rodent models (Louis et al., 2008; Micale et al., 2008; Steinberg et al., 2001).
Recurrent major depressive disorder: Imbalance of neurokinin (NK)-1 and NK-2 receptor expression in monocytes
2013, Pharmacological ResearchCitation Excerpt :In these regions, SP is co-localized with monoamine neurotransmitters, acetylcholine, GABA and glutamate, as well as other tachykinins, acting as a neurotransmitter/neuromodulator. In the rat brain, NK-2R (the preferred subtype for NKA) are present in the prefrontal cortex and the hippocampus, mainly [6]; in monkeys, Nagano et al. [7] found relevant levels of NK-2R mRNA in the prefrontal cortex, cingulate cortex and amygdala. On the contrary, NK-3R is found in the substantia nigra and ventral tegmental area, NKB being involved in the pathophysiology of schizophrenia [6].
General pathways of pain sensation and the major neurotransmitters involved in pain regulation
2018, International Journal of Molecular SciencesTachykinin NK2 receptor antagonists. A patent review (2006 - 2010)
2012, Expert Opinion on Therapeutic Patents