Skip to main content
Log in

Properties of a 125I-substance P derivative binding to synaptosomes from various brain structures and the spinal cord of the rat

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Using crude synaptosomal fractions (P2 fractions) and 125I-Bolton and Hunter substance P (125I-BHSP) as a ligand, the characteristics of specific binding sites were examined in various brain structures and in the spinal cord (dorsal and ventral parts) of the rat. Scatchard plots revealed the occurrence of a single class of binding sites in the various structures studied with comparable K d values (from 0.46 to 1.10 nmol/l in the brain and 0.51, 0.56 nmol/l in the spinal cord dorsal and ventral parts respectively) and of marked differences in the number of binding sites (Bmax) (septum > striatum > hippocampus, hypothalamus > mesencephalon > cerebral cortex and dorsal part of the spinal cord > ventral part). In the brain no correlation was found between the number of 125I-BHSP binding sites and the amount of substance P levels (substance P-like immunoreactivity) in synaptosomes, particularly in the hippocampus and the substantia nigra since the former structure was characterized by its low substance P content and its high number of binding sites and the reverse was observed in the substantia nigra. The ability of several C- and N-terminal fragments of substance P and of tachykinins to compete with 125I-BHSP binding to synaptosomes from the hippocampus, the hypothalamus and the dorsal part of the spinal cord was then determined. Results obtained were closely similar from one structure to another and comparable to those previously reported using whole brain synaptosomes. Although the presence of various types of central substance P receptors cannot be excluded, the present results indicate that only one class of sites can be demonstrated using 125I-BHSP as a ligand.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

125I-BHSP:

125I-Bolton-Hunter substance P

HPLC:

high pressure liquid chromatography

References

  • Beaujouan JC, Torrens Y, Herbert A, Daguet MC, Glowinski J, Prochiantz A (1982) Specific binding of an immunoreactive and biologically active 125I-substance P derivative to mouse mesencephalic cells in primary culture. Mol Pharmacol 22:48–55

    Google Scholar 

  • Bittiger H (1982) Substance P in the nervous system — Discussion of substance P receptors. Ciba Foundation symposium 91. Pitman Press, Great Britain, pp 193–205

    Google Scholar 

  • Bowery N (1982) Baclofen: 10 years on. Trends Pharmacol Sci 3:400–403

    Google Scholar 

  • Brownstein M, Mroz E, Kizer S, Palkovits M, Leeman S (1976) Regional distribution of substance P in the brain of the rat. Brain Res 116:299–305

    Google Scholar 

  • Couture R, Regoli D (1982) Mini review: Smooth muscle pharmacology of substance P. Pharmacology 24:1–25

    Google Scholar 

  • Engberg G, Svensson T, Rosell S, Folkers K (1981) A synthetic peptide as an antagonist of substance P. Nature 293:222–223

    Google Scholar 

  • Erspamer V (1981) The tachykinin peptide family. Trends Neurosci 4:267–269

    Google Scholar 

  • Gamse R, Holzer P, Lembeck F (1980) Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaïcin. Br J Pharmacol 68:207–213

    Google Scholar 

  • Glowinski J, Iversen L (1966) Regional studies of catecholamines in the rat brain. III. Subcellular distribution of endogenous and exogenous catecholamines in various brain regions. Biochem Pharmacol 15:977–987

    Google Scholar 

  • Gray E, Whittaker V (1962) The isolation of nerve endings from brain: an electron microscopic study of cell fragments derivated by homogenization and centrifugation. J Anat (London) 96:79–88

    Google Scholar 

  • Growcott J, Morley J, Petter M, Pinnock R, Turnbull M, Woodruff G (1980) Differences between central and peripheral actions of substance P and substance P(1-9)-nonapeptide. Proc B P S 72:504P

  • Guyenet P, Aghajanian G (1977) Excitation of neurons in the nucleus locus coeruleus by substance P and related peptides. Brain Res 136:178–184

    Google Scholar 

  • Hanley M, Sanberg B, Lee C, Iversen L, Brundish D, Wade R (1980) Specific binding of 3H-substance P to rat brain membranes. Nature 286:810–812

    Google Scholar 

  • Hökfelt T, Johansson O, Ljungdahl A, Lundberg J, Schultzberg M (1980) Peptidergic neurons. Nature 284:515–521

    Google Scholar 

  • Inagaki S, Sakanaka M, Shiosaka S, Senba E, Takagi H, Takatsuki K, Kawai Y Matsuzaki T, Iida H, Hara Y, Toyama M (1982) Experimental and immunohistochemical studies on the cerebellar substance P of the rat: localization, postnatal ontogeny and ways of entry to the cerebellum. Neuroscience 7:639–645

    Google Scholar 

  • Jessell T, Tsunoo A, Kanazawa I, Otsuka M (1979) Substance P: depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons. Brain Res 168:247–259

    Google Scholar 

  • Jones R, Olpe H (1982) A structure-activity profile of substance P and some of its fragments on supraspinal neurones in the rat. Neurosci Let 33:67–71

    Google Scholar 

  • Konishi S, Otsuka M (1974) The effects of substance P and other peptides on spinal neurons of the frog. Brain Res 65:397–410

    Google Scholar 

  • Lazarus L, Linnoila R, Hernandez O, Di Augustine R (1980) A neuropeptide in mammalian tissues with physalaemin like immunoreactivity. Nature 287:555–558

    Google Scholar 

  • Lee C, Iversen L, Hanley M, Sandberg B (1982) The possible existence of multiple receptors for substance P. Naunyn-Schmiedeberg's Arch Pharmacol 318:281–287

    Google Scholar 

  • Ljungdahl A, Hökfeld T, Nilsson G (1978) Distribution of substance P like immunoreactivity in the central nervous system of the rat. I. Cell bodies and nerve terminals. Neuroscience 3:861–943

    Google Scholar 

  • Lowry O, Rosebrough N, Farr A, Randall R (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  • Mayer N, Lembeck F, Saria A, Gamse R (1979) Substance P: characteristics of binding to synaptic vesicles of rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 306:45–51

    Google Scholar 

  • Michelot R, Leviel V, Torrens Y, Glowinski J, Cheramy A (1979) In vivo release of substance P in the cat substantia nigra. Neurosci Lett 15:141–146

    Google Scholar 

  • Michelot R, Gozlan H, Beaujouan JC, Besson MJ, Torrens Y, Glowinski J (1980) Synthesis and biological activites of substance P iodinated derivatives. Biochem Biophys Res Commun 95:491–498

    Google Scholar 

  • Ogata N, Abe H (1981) Further support for the postsynaptic action of substance P and its blockade with Baclofen in neurons of the guinea-pig hypothalamus in vitro. Exp Pharmacol 37:759–761

    Google Scholar 

  • Otsuka M, Yanagisawa M (1980) The effects of substance P and Baclofen on motoneurones of isolated spinal cord of the newborn rat. J Exp Biol 89:201–214

    Google Scholar 

  • Paxinos G, Emson P, Cuello C (1978) Substance P projections to the entopeduncular nucleus, the medial preoptic area and the lateral septum. Neurosci Lett 7:133–136

    Google Scholar 

  • Phillis J, Limacher J (1974) Excitation of cerebral cortical neurons by various polypeptides. Exp Neurol 43:414–423

    Google Scholar 

  • Piercey M, Einspahr F (1980) Use of substance P partial fragments to characterize substance P receptors of cat dorsal horn neurons. Brain Res 187:481–486

    Google Scholar 

  • Rosell S, Folkers K (1982) Substance P-antagonists: a new type of pharmacological tool. Tends Pharmacol Sci 3:211–212

    Google Scholar 

  • Sakanaka M, Shiosaka S, Takatsuki K, Inagaki S, Takagi H, Senba E, Kawai Y, Matsusaki T, Tohyama M (1981) Experimental immunohistochemical studies on the amygdalofugal peptidergic (substance P and somatostatin) fibers in the stria terminalis of the rat. Brain Res 221:231–242

    Google Scholar 

  • Salt T, DeVries G, Rodriguez R, Cahusac P, Morris R, Hill R (1982) Evaluation of (d-Pro2, d-Trp7, 9). Substance P as an antagonist of substance P response in the rat central nervous system. Neurosci Lett 30:291–295

    Google Scholar 

  • Senba E, Shiosaka S, Hara Y, Inagaki S, Sakanaka M, Takatsuki K, Kawai Y, Toyama M (1982) Ontogeny of the peptidergic system in the rat spinal cord; immunohistochemical analysis. J Comp Neurol 208:54–66

    Google Scholar 

  • Somogyi P, Priestly J, Cuello A, Smith A, Bolam J (1982) Synaptic connections of substance P-immunoreactive nerve terminals in the substantia nigra of the rat. Cell Tissues Res 223:469–486

    Google Scholar 

  • Snyder S (1975) Neurotransmitter and drug receptors in the brain. Biochem Pharmacol 24:1371–1374

    Google Scholar 

  • Viger A, Beaujouan JC, Torrens Y, Glowinski J (1983) Specific binding of a (125I) substance P derivative to rat brain synaptosomes. J Neurochem 40:1030–1039

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torrens, Y., Beaujouan, J.C., Viger, A. et al. Properties of a 125I-substance P derivative binding to synaptosomes from various brain structures and the spinal cord of the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 324, 134–139 (1983). https://doi.org/10.1007/BF00497019

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00497019

Key words

Navigation