Elsevier

Neuroscience

Volume 116, Issue 3, 17 February 2003, Pages 761-773
Neuroscience

Original contribution
Autoradiographic distribution of tachykinin NK2 binding sites in the rat brain: comparison with NK1 and NK3 binding sites

https://doi.org/10.1016/S0306-4522(02)00748-0Get rights and content

Abstract

The autoradiographic distribution of tachykinin NK2 binding sites was determined in the adult rat brain using [125I]neurokinin A in the presence of either senktide (NK3 agonist) and [Pro9]substance P (NK1 agonist) or senktide and SR 140333 (NK1 antagonist). Indeed, this radioligand labels two subtypes of NK1 binding sites (which present a high affinity not only for SP but also for neurokinin A, neuropeptide K and neuropeptide γ) as well as NK3 binding sites. The distribution of NK2 binding sites was also compared with those of NK1 and NK3 binding sites, these sites being labeled with [125I]Bolton and Hunter substance P and [125I]Bolton and Hunter eledoisin, respectively. In agreement with our results obtained with membranes from various brain structures, NK2-sensitive [125I]neurokinin A labeling was mainly observed in few structures including the dorsal and ventral hippocampus, the septum, the thalamus and the prefrontal cortex. The density of NK2 binding sites was weak when compared with those of NK1 and NK3 binding sites. Marked differences were observed in the distributions of NK1, NK2 and NK3 binding sites. These results are discussed taking into consideration differences or similarities between the distributions of NK2-sensitive [125I]neurokinin A binding sites and of their endogenous ligands (neurokinin A, neuropeptide K and neuropeptide γ) but also local NK2 agonist responses blocked by NK2 antagonists. Insights on the roles of endogenous tachykinins in several brain functions are also discussed on the basis of the respective distributions of different neurokinin binding sites.

Section snippets

Subjects

Male Sprague–Dawley rats (200–250 g; Charles River, Cléon, France) were housed in groups of five with food and water ad libitum in a room maintained at 22 °C with 12-h/12-h light/dark cycle. Animals were treated in accordance with the Guide for Care and Use of Laboratory Animals established by the National Institute of Health (NIH 80-23) and with the European Community Council Directive (86/609/EEC).

Ligands and drugs

[125I]NKA (2000 Ci/mmol) was from Amersham. [125I]Bolton and Hunter substance P ([125I]BHSP) and

Regional distribution of NK2-sensitive [125I]NKA binding sites

Brain sections were incubated with [125I]NKA (50 pM) in the presence of either senktide (1 μM, NK3 agonist) and SR 140333 (0.1 μM, NK1 antagonist; n=5) or senktide and [Pro9]SP (1 μM, NK1 agonist; n=3) to completely avoid labeling of NK3 and NK1 binding sites. For each area and in both conditions, the specific NK2 component of [125I]NKA total binding corresponds to the binding inhibited by 1 μM NKA or 0.1 μM SR 48968. Except in the cerebral cortex and the cerebellum, nonspecific binding was

Discussion

The autoradiographic distribution of tachykinin NK2 binding sites was determined in the brain of the adult rat using the agonist [125I]NKA, a ligand with a much higher specific radioactivity than tritiated ligands such as the antagonists [3H]SR 48968 or [3H]GR 100679. [125I]NKA labels two subtypes of NK1 binding sites (which present a high affinity not only for SP but also for NKA, NPK and NPγ) as well as NK3 binding sites in the rat brain (Beaujouan et al., 2000). Labeling of these NK1 and NK3

Acknowledgements

We would like to thank J. Prémont, A-M. Thierry and J-M. Deniau for fruitful discussions, A. M. Godeheu, J-P. Martin and P. Llegou for histological, photographic and photomontage assistance, respectively.

References (63)

  • G. Griebel et al.

    Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery

    Neurosci Biobehav Rev

    (2001)
  • S. Guard et al.

    Tachykinin receptor typesclassification and membrane signalling mechanisms

    Neurochem Int

    (1991)
  • R.M. Hagan et al.

    Characterisation, CNS distribution and function of NK2 receptors studied using potent NK2 receptor antagonists

    Regul Pept

    (1993)
  • X. Langlois et al.

    Detailed distribution of neurokinin 3 receptors in the rat, guinea pig and gerbil braina comparative autoradiographic study

    Neuropharmacology

    (2001)
  • N. Lindefors et al.

    Neuroleptic treatment induces region-specific changes in levels of neurokinin A and substance P in rat brain

    Neuropeptides

    (1986)
  • N. Lindefors et al.

    Amphetamine facilitates the in vivo release of neurokinin A in the nucleus accumbens of the rat

    Eur J Pharmacol

    (1989)
  • C.A. Maggi

    Principles of tachykininergic co-transmission in the peripheral and enteric nervous system

    Regul Pept

    (2000)
  • C.A. Maggi et al.

    The dual nature of the tachykinin NK1 receptor

    Trends Pharmacol Sci

    (1997)
  • M.M. Marcus et al.

    Effect of chronic antipsychotic drug treatment on preprosomatostatin and preprotachykinin A mRNA levels in the medial prefrontal cortex, the nucleus accumbens and the caudate putamen of the rat

    Brain Res Mol Brain Res

    (1997)
  • F. Martini-Luccarini et al.

    Effects of tachykinins on identified dorsal vagal neuronsan electrophysiological study in vitro

    Neuroscience

    (1996)
  • D. Mileusnic et al.

    Neurokinin-3 receptor distribution in rat and human brainan immunohistochemical study

    Neuroscience

    (1999)
  • T. Palanche et al.

    The neurokinin A receptor activates calcium and cAMP responses through distinct conformational states

    J Biol Chem

    (2001)
  • F. Petitet et al.

    Possible existence of a new tachykinin receptor subtype in the guinea pig ileum

    Peptides

    (1992)
  • C. Polidori et al.

    Further evidence that central tachykinin NK-1 receptors mediate the inhibitory effect of tachykinins on angiotensin-induced drinking in rats

    Peptides

    (1998)
  • M. Saffroy et al.

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

    Peptides

    (1988)
  • C.W. Shults et al.

    Comparison of substance K-like and substance P-like fibers and cells in the rat hippocampus

    Brain Res

    (1987)
  • C.W. Shults et al.

    A comparison of the anatomical distribution of substance P and substance P receptors in the rat central nervous system

    Peptides

    (1984)
  • G. Sperk et al.

    Differential changes in tachykinins after kainic acid-induced seizures in the rat

    Neuroscience

    (1990)
  • R. Steinberg et al.

    Facilitation of striatal acetylcholine release by dopamine D1 receptor stimulationinvolvement of enhanced nitric oxide production via neurokinin-2 receptor activation

    Neuroscience

    (1998)
  • A.J. Stoessl et al.

    Autoradiographic visualization of NK-3 tachykinin binding sites in the rat brain, utilizing [3H]senktide

    Brain Res

    (1990)
  • Y. Takeda et al.

    Regional distribution of neuropeptide gamma and other tachykinin peptides derived from the substance P gene in the rat

    Regul Pept

    (1990)
  • Cited by (120)

    • Neuroanatomical relationship between the cholinergic and tachykininergic systems in the adult human brainstem: An immunohistochemical study

      2019, Journal of Chemical Neuroanatomy
      Citation Excerpt :

      The three endogenous tachykinins SP, NKA and NKB exhibit preferential (but not exclusive) binding for the tachykinin receptors NK1, NK2 and NK3 respectively (Saffroy et al., 2003; Page, 2005; Schable et al., 2012). The distribution patterns of the different NK receptors do not always match with that of their respective ligands: for example, it has been reported that a region rich in NKA such as the striatum is practically devoid of NK2 receptors (Saffroy et al., 2003). Comparing the distributions of the three receptors they display also marked differences, since structures rich in NK1 and NK3 binding sites are devoid of NK2 binding sites (Saffroy et al., 2003).

    • Tachykinin NK1 receptor antagonist L-733,060 and substance P deletion exert neuroprotection through inhibiting oxidative stress and cell death after traumatic brain injury in mice

      2019, International Journal of Biochemistry and Cell Biology
      Citation Excerpt :

      NK receptors are 7-transmembrane domain, G-protein-coupled receptors, with three, known as the NK1, NK2, and NK3 receptor, having been identified to date (Maggi, 1995). SP normally has the highest affinity for the NK1 receptor, and the predominance of the NK1 receptor is in the adult brain (Saffroy et al., 2003). The present study showed that a significant increase of NK1R protein levels following TBI was observed both in the wild type and the SP knock out mice, but there was no significantly difference in the expression of NK1R at 24 h post-TBI between these two groups, indicating upregulation of NK1R is a consequence of TBI, independent of the levels of substance P.

    View all citing articles on Scopus
    View full text