Skip to main content
SpringerLink
Log in

High-affinity Neurotensin Receptor is Involved in Phosphoinositide Turnover Increase by Inhibition of Sodium Pump in Neonatal Rat Brain

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Phosphoinositide (PI) metabolism is enhanced in neonatal brain by activation of neurotransmitter receptors and by inhibition of the sodium pump with ouabain or endogenous inhibitor termed endobain E. Peptide neurotensin inhibits synaptosomal membrane Na+, K+-ATPase activity, an effect blocked by SR 48692, a selective antagonist for high-affinity neurotensin receptor (NTS1). The purpose of this study was to evaluate potential participation of NTS1 receptor on PI hydrolysis enhancement by sodium pump inhibition. Cerebral cortex miniprisms from neonatal Wistar rats were preloaded with [3H]myoinositol in buffer during 60 min and further preincubated for 0 min or 30 min in the absence or presence of SR 48692. Then, ouabain or endobain E were added and incubation proceeded during 20 or 60 min. Reaction was stopped with chloroform/methanol and [3H]inositol-phosphates (IPs) accumulation was quantified in the water phase. After 60-min incubation with ouabain, IPs accumulation values reached roughly 500% or 860% in comparison with basal values (100%), if the preincubation was omitted or lasted 30 min, respectively. Values were reduced 50% in the presence of SR 48692. In 20-min incubation experiments, IPs accumulation by ouabain versus basal was 300% or 410% if preincubation was 0 min or 30 min, respectively, an effect blocked 23% or 32% with SR 48692. PI hydrolysis enhancement by endobain E was similarly blocked by SR 48692, being this effect higher when sample incubation with the endogenous inhibitor lasted 60 min versus 20 min. Present results indicate that PI hydrolysis increase by sodium pump inhibition with ouabain or endobain E is partially diminished by SR 48692. It is therefore suggested that NTS1 receptor may be involved in cell signaling system mediated by PI turnover.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Fain JN, Wallace MA, Wojcikiewicz RJ (1988) Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones. FASEB J 2:2569–2574

    PubMed  CAS  Google Scholar 

  2. Fain JN (1990) Regulation of phosphoinositide-specific phospholipase C. Biochim Biophys Acta 1053:81–88

    Article  PubMed  CAS  Google Scholar 

  3. Balduini W, Candura SM, Costa LG (1991) Regional development of carbachol-, glutamate-, norepinephrine-, and serotonine-stimulated phosphoinositide metabolism in rat brain. Dev Brain Res 62:115–120

    Article  CAS  Google Scholar 

  4. Vincent J-P, Mazella J, Kitabgi P (1999) Neurotensin and neurotensin receptors. Trends Pharmacol Sci 20:302–309

    Article  PubMed  CAS  Google Scholar 

  5. Vincent JP (1992) Neurotensin receptors. Binding properties, transduction mechanisms, and purification. Ann NY Acad Sci 668:90–100

    Article  PubMed  CAS  Google Scholar 

  6. Gully D, Canton M, Boigegrain R et al (1993) Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc Natl Acad Sci USA 90:65–69

    Article  PubMed  CAS  Google Scholar 

  7. Pereyra-Alfonso S, López Ordieres MG, Armanino MV et al (2005) High-affinity neurotensin receptor is involved in phosphoinositide hydrolysis stimulation by carbachol in neonatal rat brain. Dev Brain Res 154:247–254

    Article  CAS  Google Scholar 

  8. Stahl W (1986) The Na,K-ATPase of nervous tissue. Neurochem Int 8:449–476

    Article  CAS  Google Scholar 

  9. Albers RW, Siegel GJ (2006) Membrane transport. In: Siegel GJ, Albers RW, Brady ST et al (eds) Basic neurochemistry. Molecular, cellular, and medical aspects, 7th edn. Elsevier Academic Press, MA, pp 73–94

    Google Scholar 

  10. Goto A, Yamada K, Yagi N et al (1992) Physiology and pharmacology of endogenous digitalis-like factors. Pharmacol Rev 44:377–399

    PubMed  CAS  Google Scholar 

  11. Rodríguez de Lores Arnaiz G (1992) In search of synaptosomal Na+, K+-ATPase regulators. Mol Neurobiol 6:359–375

    Article  PubMed  Google Scholar 

  12. Rodríguez de Lores Arnaiz G (2000) How many endobains are there? Neurochem Res 25:1421–1430

    Article  PubMed  Google Scholar 

  13. Schöner W (2002) Endogenous cardiac glycosides, a new class of steroid hormones. Eur J Biochem 269:2440–2448

    Article  PubMed  CAS  Google Scholar 

  14. Rodríguez de Lores Arnaiz G, Antonelli de Gómez de Lima M (1986) Partial characterization of an endogenous factor which modulates the effect of catecholamines on synaptosomal Na+, K+-ATPase. Neurochem Res 11:933–947

    Article  PubMed  Google Scholar 

  15. Rodríguez de Lores Arnaiz G, Peña C (1995) Characterization of synaptosomal membrane Na+, K+-ATPase inhibitors. Neurochem Int 27:319–327

    Article  PubMed  Google Scholar 

  16. Peña C, Rodríguez de Lores Arnaiz G (1997) Differential properties between an endogenous brain Na+, K+-ATPase inhibitor and ouabain. Neurochem Res 22:379–383

    Article  PubMed  Google Scholar 

  17. Rodríguez de Lores Arnaiz G, Reinés A, Herbin T et al (1998) Na+, K+-ATPase interaction with a brain endogenous inhibitor (endobain E). Neurochem Int 33:425–433

    Article  PubMed  Google Scholar 

  18. Vatta M, Peña C, Fernández B et al (1999) A brain Na+, K+-ATPase inhibitor (endobain E) enhances norepinephrine release in rat hypothalamus. Neuroscience 90:573–579

    Article  PubMed  CAS  Google Scholar 

  19. Balduini W, Costa LG (1990) Characterization of ouabain-induced phosphoinositide hydrolysis in brain slices of the neonatal rat. Neurochem Res 15:1023–1030

    Article  PubMed  CAS  Google Scholar 

  20. Calviño MA, Peña C, Rodríguez de Lores Arnaiz G (2001) An endogenous Na+, K+-ATPase inhibitor enhances phosphoinositide hydrolysis in neonatal but not in adult rat brain cortex. Neurochem Res 26:1253–1259

    Article  PubMed  Google Scholar 

  21. Berridge MJ, Downes CP, Hanley MR (1982) Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 206:587–595

    PubMed  CAS  Google Scholar 

  22. Brown E, Kendall DA, Nahorski SR (1984) Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterization. J Neurochem 42:1379–1387

    Article  PubMed  CAS  Google Scholar 

  23. Berridge MJ (1987) Inositol triphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem 56:159–193

    PubMed  CAS  Google Scholar 

  24. Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  25. Rodríguez de Lores Arnaiz G (1993) An endogenous factor which interacts with synaptosomal membrane Na+, K+-ATPase activation by K+. Neurochem Res 18:655–661

    Article  PubMed  Google Scholar 

  26. Hermans E, Jeanjean AP, Laduron PM et al (1993) Postnatal ontogeny of the rat brain neurotensin receptor mRNA. Neurosci Lett 157:45–48

    Article  PubMed  CAS  Google Scholar 

  27. Mazella J, Botto JM, Guillemare E et al (1996) Structure, functional expression, and cerebral localization of the levocabastine-sensitive neurotensin/neuromedin N receptor from mouse brain. J Neurosci 16:5613–5620

    PubMed  CAS  Google Scholar 

  28. Sato M, Kiyama H, Tohyama M (1992) Different postnatal development of cells expressing mRNA encoding neurotensin receptor. Neuroscience 48:137–149

    Article  PubMed  CAS  Google Scholar 

  29. Lépée-Lorgeoux I, Betancur C, Souazé F, Rostène W, Bérod A, Pélaprat D (2000) Regulation of the neurotensin NT1 receptor in the developing rat brain following chronic treatment with the antagonist SR 48692. J Neurosc Res 60:362–369

    Article  Google Scholar 

  30. Abdel-Latif AA, Brody J, Ramahi H (1967) Studies on sodium-potassium adenosine triphosphatase of the nerve endings and appearance of electrical activity in developing rat brain. J Neurochem 14:1133–1141

    Article  PubMed  CAS  Google Scholar 

  31. Kissane JQ, Hawrylewicz EJ (1975) Development of Na+, K+-ATPase in neonatalrat brain synaptosomes after perinatal protein malnutrition. Pediatr Res 9:146–150

    Article  PubMed  CAS  Google Scholar 

  32. Samson FE Jr, Quinn DJ (1978) Na+, K+-activated ATPase in rat brain development. J Neurochem 14:421–427

    Article  Google Scholar 

  33. Bertoni JM, Siegel GJ (1978) Development of (Na+-K+)-ATPase in rat cerebrum: correlation with Na+-dependent phosphorylation and K+-paranitrophenyl-phosphatase. J Neurochem 31:1501–1511

    Article  PubMed  CAS  Google Scholar 

  34. Schmitt CA, McDonough AA (1986) Developmental and thyroid hormone regulation of two molecular forms of Na+, K+-ATPase in brain. J Biol Chem 261:10439–10444

    PubMed  CAS  Google Scholar 

  35. Schmitt CA, McDonough AA (1988) Thyroid hormone regulates alpha and alpha + isoforms of Na,K-ATPase during development in neonatal ral brain. J Biol Chem 263:17643–17649

    PubMed  CAS  Google Scholar 

  36. Calviño MA, Peña C, Rodríguez de Lores Arnaiz G (2002) Metabotropic glutamate receptor involvement in phosphoinositide hydrolysis stimulation by an endogenous Na+, K+-ATPase inhibitor and ouabain in neonatal rat brain. Dev Brain Res 138:167–175

    Article  Google Scholar 

  37. Vignes M, Blanc E, Davos F et al (1996) Cadmium rapidly and irreversibly blocks presynaptic phospholipase C-linked metabotropic glutamate receptors. Neurochem Int 29:371–381

    Article  PubMed  CAS  Google Scholar 

  38. Vignes M, Blanc E, Sassetti I et al (1996) Intra-vs extracellular calcium regulation of neurotransmitter-stimulated phosphoinositide breakdown. Neurochem Int 28:145–153

    Article  PubMed  CAS  Google Scholar 

  39. López Ordieres MG, Rodríguez de Lores Arnaiz G (2000) Neurotensin inhibits neuronal Na+, K+-ATPase activity through high affinity peptide receptor. Peptides 21:571–576

    Article  PubMed  Google Scholar 

  40. López Ordieres MG, Rodríguez de Lores Arnaiz G (2002) Neurotensin effect on Na+, K+-ATPase is CNS area- and membrane-dependent and involves high affinity NT1 receptor. Neurochem Res 27:1547–1553

    Google Scholar 

  41. Reichelt W, Dettmer D, Bruckner G et al (1989) Potassium as a signal for both proliferation and differentiation of rabbit retinal (Muller) glia growing in cell culture. Cell Signal 1:187–194

    Article  PubMed  CAS  Google Scholar 

  42. Matsuda T, Murata Y, Kawamura N et al (1993) Selective induction of alpha 1 isoform of (Na+ + K+)-ATPase by insulin/insulin-like growth factor-I in cultured rat astrocytes. Arch Biochem Biophys 307:175–182

    Article  PubMed  CAS  Google Scholar 

  43. Xie Z, Askari A (2002) Na(+)/K(+)-ATPase as a signal transducer. Eur J Biochem 269:2434–2439

    Article  PubMed  CAS  Google Scholar 

  44. Aizman O, Aperia A (2003) Na,K-ATPase as a signal transducer. Ann NY Acad Sci 986:489–496

    Article  PubMed  CAS  Google Scholar 

  45. Xie Z (2003) Molecular mechanisms of Na/K-ATPase-mediated signal transduction. Ann NY Acad Sci 986:497–503

    PubMed  CAS  Google Scholar 

  46. Wang H, Haas M, Liang M et al (2004) Ouabain assembles signaling cascades through the caveolar Na+/K+-ATPase. J Biol Chem 279:17250–17259

    Article  PubMed  CAS  Google Scholar 

  47. Liu J, Liang M, Liu L et al (2005) Ouabain induced endocytosis of the plasmalemmal Na/K-ATPase in LLC-PK1 cells requires caveolin-1. Kidney Int 67:1844–1854

    Article  PubMed  CAS  Google Scholar 

  48. Galbiati F, Razani B, Lisanti MP (2001) Emerging themes in lipid rafts and caveolae. Cell 106:403–411

    Article  PubMed  CAS  Google Scholar 

  49. Liu J, Periyasamy SM, Gunning W et al (2002) Effects of cardiac glycosides on sodium pump expression and function in LLC-PK1 and MDCK cells. Kidney Int 62:2118–2125

    Article  PubMed  CAS  Google Scholar 

  50. Nabi IR, Le PU (2003) Caveolae/raft-dependent endocytosis. J Cell Biol 161:673–677

    Article  PubMed  CAS  Google Scholar 

  51. Hope HR, Pike LJ (1996) Phosphoinositides and phosphoinositide-utilizing enzymes in detergent-insoluble lipid domains. Mol Biol Cell 7:843–851

    PubMed  CAS  Google Scholar 

  52. Pike LJ, Casey L (1996) Localization and turnover of phosphatidylinositol 4,5-bisphosphate in caveolin-enriched membrane domains. J Biol Chem 271:26453–26456

    Article  PubMed  CAS  Google Scholar 

  53. Fujimoto T, Nakade S, Miyawaki A et al (1992) Localization of inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae. J Cell Biol 119:1507–1514

    Article  PubMed  Google Scholar 

  54. Rodríguez de Lores Arnaiz G, Alberici M, De Robertis E (1967) Ultrastructural and enzymic studies of cholinergic and non-cholinergic synaptic membranes isolated from brain cortex. J Neurochem 14:215–225

    Article  Google Scholar 

  55. Bai M (2004) Dimerization of G-protein-coupled receptors: roles in signal transduction. Cell Signal 16:175–186

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

G. R. de L. A. and C. P. are chief investigators from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). The authors are indebted to Agencia Nacional de Promoción Científica y Tecnológica, CONICET and Universidad de Buenos Aires, Argentina, as well as to Committee for Aid and Education, International Society for Neurochemistry (CAEN, ISN), for financial support.

Author information

Authors and Affiliations

  1. Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis”, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121, Buenos Aires, Argentina

    Susana Pereyra-Alfonso, María del Valle Armanino, Carolina Vázquez & Georgina Rodríguez de Lores Arnaiz

  2. IQUIFIB-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113, Buenos Aires, Argentina

    Clara Peña

  3. Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113, Buenos Aires, Argentina

    Georgina Rodríguez de Lores Arnaiz

Authors
  1. Susana Pereyra-Alfonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María del Valle Armanino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carolina Vázquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Clara Peña
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Georgina Rodríguez de Lores Arnaiz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georgina Rodríguez de Lores Arnaiz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pereyra-Alfonso, S., del Valle Armanino, M., Vázquez, C. et al. High-affinity Neurotensin Receptor is Involved in Phosphoinositide Turnover Increase by Inhibition of Sodium Pump in Neonatal Rat Brain. Neurochem Res 33, 2206–2213 (2008). https://doi.org/10.1007/s11064-008-9672-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-008-9672-2

Keywords

Search

Navigation