Skip to main content
SpringerLink
Log in
Book cover

Microdialysis Techniques in Neuroscience pp 275–298Cite as

Indirect Analysis of Nitric Oxide and Quantitation of Selective Nitric Oxide Synthase Inhibitors in Microdialysate Samples

  • Protocol
  • First Online:

  • 781 Accesses

Part of the book series: Neuromethods ((NM,volume 75))

Abstract

While a longstanding body of evidence has suggested that nitric oxide plays a key role in maintaining vascular tone, work over the last decade has indicated that nitric oxide also is an important messenger in the central nervous system. Due to the extremely labile nature of this molecule, quantitation in bulk brain tissue is problematic. Indirect methods of analysis, therefore, have been developed, with the use of microdialysis technology for sample collection. To probe the physiologic and pharmacologic importance of nitric oxide, a variety of nitric oxide synthase inhibitors also have been identified and are amenable to quantitative analysis by standard chromatographic techniques in brain tissue microdialysate. The use of the microdialysis approach for the combined purpose of measuring concentrations of nitric oxide synthase inhibitors at the site of action and changes in nitric oxide content at that site illustrates the power of microdialysis in studies designed to elucidate the linkage between drug concentration (pharmacokinetics) and drug action (pharmacodynamics). This chapter is intended to describe the experimental design, procedural issues, and types of data associated with the use of brain microdialysis to explore the role of nitric oxide in central nervous system pharmacokinetics and pharmacodynamics.

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

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Viswanathan CT, Bansal S, Booth B et al (2007) Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays. Pharm Res 24:1962–1973

    Article  PubMed  CAS  Google Scholar 

  2. Holford NH, Sheiner LB (1981) Pharmacokinetic and pharmacodynamic modeling in vivo. Crit Rev Bioeng 5:273–322

    PubMed  CAS  Google Scholar 

  3. Mager DE, Jusko WJ (2008) Development of translational pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther 83:909–912

    Article  PubMed  CAS  Google Scholar 

  4. Zhou Q, Gallo JM (2011) The pharmacokinetic/pharmacodynamic pipeline: translating anticancer drug pharmacology to the clinic. AAPS J 13:111–120

    Article  PubMed  Google Scholar 

  5. Höcht C, Opezzo JA, Bramuglia GF et al (2006) Application of microdialysis in clinical pharmacology. Curr Clin Pharmacol 1:163–183

    Article  PubMed  Google Scholar 

  6. Helmy A, Carpenter KL, Hutchinson PJ (2007) Microdialysis in the human brain and its potential role in the development and clinical assessment of drugs. Curr Med Chem 14:1525–1537

    Article  PubMed  CAS  Google Scholar 

  7. Blakeley J, Portnow J (2010) Microdialysis for assessing intratumoral drug disposition in brain cancers: a tool for rational drug development. Expert Opin Drug Metab Toxicol 6:1477–1491

    Article  PubMed  CAS  Google Scholar 

  8. Barbosa RM, Lourenço CF, Santos RM et al (2008) In vivo real-time measurement of nitric oxide in anesthetized rat brain. Methods Enzymol 441:351–367

    Article  PubMed  CAS  Google Scholar 

  9. Moncada S, Palmer RM, Higgs EA (1989) Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 38:1709–1715

    Article  PubMed  CAS  Google Scholar 

  10. Bauer V, Sotníková R (2010) Nitric oxide—the endothelium-derived relaxing factor and its role in endothelial functions. Gen Physiol Biophys 29:319–340

    Article  PubMed  CAS  Google Scholar 

  11. Stokes GS (2006) Nitrates as adjunct hypertensive treatment. Curr Hypertens Rep 8:60–68

    Article  PubMed  CAS  Google Scholar 

  12. Hara S, Mukai T, Kurosaki K, Mizukami H et al (2004) Different response to exogenous L-arginine in nitric oxide production between hippocampus and striatum of conscious rats: a microdialysis study. Neurosci Lett 366:302–307

    Article  PubMed  CAS  Google Scholar 

  13. Gören MZ, Aricioglu-Kartal F, Yurdun T et al (2001) Investigation of extracellular L-citrulline concentration in the striatum during alcohol withdrawal in rats. Neurochem Res 12:1327–1333

    Article  Google Scholar 

  14. Nowak P, Brus R, Oswiecimska J et al (2002) 7-Nitroindazole enhances amphetamine-evoked dopamine release in rat striatum. An in vivo microdialysis and voltammetric study. J Physiol Pharmacol 53:251–263

    PubMed  CAS  Google Scholar 

  15. Pepicelli O, Raiteri M, Fedele E (2004) The NOS/sGC pathway in the rat central nervous system: a microdialysis overview. Neurochem Int 45:787–797

    Article  PubMed  CAS  Google Scholar 

  16. Hong SK, Jung IS, Bang SA et al (2006) Effect of nitric oxide synthase inhibitor and NMDA receptor antagonist on the development of nicotine sensitization of nucleus accumbens dopamine release: an in vivo microdialysis study. Neurosci Lett 409:220–223

    Article  PubMed  CAS  Google Scholar 

  17. Chalimoniuk M, Langfort J (2007) The effect of subchronic, intermittent L-DOPA treatment on neuronal nitric oxide synthase and soluble guanylyl cyclase expression and activity in the striatum and midbrain of normal and MPTP-treated mice. Neurochem Int 50:821–833

    Article  PubMed  CAS  Google Scholar 

  18. Raimondi L, Alfarano C, Pacini A et al (2007) Methylamine-dependent release of nitric oxide and dopamine in the CNS modulates food intake in fasting rats. Br J Pharmacol 150:1003–1010

    Article  PubMed  CAS  Google Scholar 

  19. Llansola M, Hernandez-Viadel M, Erceg S et al (2009) Increasing the function of the glutamate-nitric oxide-cyclic guanosine monophosphate pathway increases the ability to learn a Y-maze task. J Neurosci Res 87:2351–2355

    Article  PubMed  CAS  Google Scholar 

  20. Li S, Wang W, Wang C et al (2010) Possible involvement of NO/NOS signaling in hippocampal amyloid-β production induced by transient focal cerebral ischemia in aged rats. Neurosci Lett 470:106–110

    Article  PubMed  CAS  Google Scholar 

  21. Saulskaya NB, Fofonova NV, Sudorgina PV (2010) Activation of the noergic system of the nucleus accumbens on presentation of contextual danger signals. Neurosci Behav Physiol 40:907–912

    Article  PubMed  CAS  Google Scholar 

  22. Kalinchuk AV, McCarley RW, Porkka-Heiskanen T et al (2011) The time course of adenosine, nitric oxide (NO), and inducible NO synthase in the brain with sleep loss and their role in the non-rapid eye movement sleep homeostatic cascade. J Neurochem 116:260–272

    Article  PubMed  CAS  Google Scholar 

  23. Koizumi H, Fujisawa H, Suehiro E et al (2011) Neuroprotective effects of Ebselen following forebrain ischemia: involvement of glutamate and nitric oxide. Neurol Med Chir (Tokyo) 51:337–343

    Article  Google Scholar 

  24. Karlsson GA, Chaitoff KA, Hossain S et al (2007) Modulation of cardiovascular responses and neurotransmission during peripheral nociception following nNOS antagonism within the periaqueductal gray. Brain Res 1143:150–160

    Article  PubMed  CAS  Google Scholar 

  25. Zelinski LM, Ohgami Y, Chung E et al (2009) A prolonged nitric oxide-dependent, opioid-mediated antinociceptive effect of hyperbaric oxygen in mice. J Pain 10:167–172

    Article  PubMed  CAS  Google Scholar 

  26. Toda N, Kishioka S, Hatano Y et al (2009) Modulation of opioid actions by nitric oxide signaling. Anesthesiology 110:166–181

    Article  PubMed  CAS  Google Scholar 

  27. Abdel-Zaher AO, Abdel-Rahman MS, Elwasei FM (2010) Blockade of nitric oxide overproduction and oxidative stress by Nigella sativa oil attenuates morphine-induced tolerance and dependence in mice. Neurochem Res 35:1557–1565

    Article  PubMed  CAS  Google Scholar 

  28. Horton TL, Pollack GM (1991) Enterohepatic recirculation and renal metabolism of morphine in the rat. J Pharm Sci 80:1147–1152

    Article  PubMed  CAS  Google Scholar 

  29. Dagenais C, Zong J, Ducharme J et al (2001) Effect of mdr1a P-glycoprotein gene disruption, gender, and substrate concentration on brain uptake of selected compounds. Pharm Res 18:957–963

    Article  PubMed  CAS  Google Scholar 

  30. Dagenais C, Graff CL, Pollack GM (2004) Variable modulation of opioid brain uptake by P-glycoprotein in mice. Biochem Pharmacol 67:269–276

    Article  PubMed  CAS  Google Scholar 

  31. Kalvass JC, Olson ER, Cassidy MP et al (2007) Pharmacokinetics and pharmacodynamics of seven opioids in P-glycoprotein-competent mice: assessment of unbound brain EC50, u and correlation of in vitro, preclinical, and clinical data. J Pharmacol Exp Ther 323:346–355

    Article  PubMed  CAS  Google Scholar 

  32. Chen C, Pollack GM (1997) Blood-brain disposition and antinociceptive effects of d-penicillamine2,5-enkephalin in the mouse. J Pharmacol Exp Ther 283:1151–1159

    PubMed  CAS  Google Scholar 

  33. Chen C, Pollack GM (1998) Altered disposition and antinociception of (d-penicillamine(2,5)) enkephalin in mdr1a-gene-deficient mice. J Pharmacol Exp Ther 287:545–552

    PubMed  CAS  Google Scholar 

  34. Bauer B, Yang X, Hartz AM et al (2006) In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation. Mol Pharmacol 70:1212–1219

    Article  PubMed  CAS  Google Scholar 

  35. Ouellet DM, Pollack GM (1995) A pharmacokinetic-pharmacodynamic model of tolerance to morphine analgesia during infusion in rats. J Pharmacokinet Biopharm 23:531–549

    PubMed  CAS  Google Scholar 

  36. Ouellet DM, Pollack GM (1997) Pharmacodynamics and tolerance development during multiple intravenous bolus morphine administration in rats. J Pharmacol Exp Ther 281:713–720

    PubMed  CAS  Google Scholar 

  37. Heinzen EL, Pollack GM (2004) Pharmacodynamics of morphine-induced neuronal nitric oxide production and antinociceptive tolerance development. Brain Res 1023:175–184

    Article  PubMed  CAS  Google Scholar 

  38. Heinzen EL, Pollack GM (2004) The development of morphine antinociceptive tolerance in nitric oxide synthase-deficient mice. Biochem Pharmacol 67:735–741

    Article  PubMed  CAS  Google Scholar 

  39. Stamler JS, Feelisch M (1996) Methods in nitric oxide research. Wiley, New York

    Google Scholar 

  40. Bush MA, Pollack GM (2000) Pharmacokinetics and protein binding of the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole. Biopharm Drug Dispos 21:221–228

    Article  PubMed  CAS  Google Scholar 

  41. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, New York

    Google Scholar 

  42. Colin A-K (1988) Microdialysis user’s guide, 4th edn. Carnegie Medicin, Stockholm

    Google Scholar 

  43. Maragos CM, Morley D, Wink DA et al (1991) Complexes of NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects. J Med Chem 34:3242–3247

    Article  PubMed  CAS  Google Scholar 

  44. Fukuto JM, Hobbs AJ, Ignarro LJ (1993) Conversion of nitroxyl (HNO) to nitric oxide (NO) in biological systems: the role of physiological oxidants and relevance to the biological activity of HNO. Biochem Biophys Res Commun 196:707–713

    Article  PubMed  CAS  Google Scholar 

  45. Lee S-C, Wang J-J, Ho S-T et al (1997) Nalbuphine coadministered with morphine prevents tolerance and dependence. Anesth Analg 84:810–815

    PubMed  CAS  Google Scholar 

  46. Chen SW, Maguire PA, Davies MF et al (1996) Evidence for mu1-opioid receptor involvement in fentanyl-mediated respiratory depression. Eur J Pharmacol 312:241–244

    Article  PubMed  CAS  Google Scholar 

  47. Roy S, Liu HC, Loh HH (1998) mu-opioid receptor-knockout mice: the role of mu-opioid receptor in gastrointestinal transit. Brain Res Mol Brain Res 56:281–283

    Article  PubMed  CAS  Google Scholar 

  48. Culpepper-Morgan JA, Holt PR, LaRoche D et al (1995) Orally administered opioid antagonists. Neurosci Lett 56:1187–1192

    CAS  Google Scholar 

  49. Bourne JA (2003) Intracerebral microdialysis: 30 years as a tool for the neuroscientist. Clin Exp Pharmacol Physiol 30:16–24

    Article  PubMed  CAS  Google Scholar 

  50. Cano-Cebrián MJ, Zornoza T, Polache A et al (2005) Quantitative in vivo microdialysis in pharmacokinetic studies: some reminders. Curr Drug Metab 6:83–90

    Article  PubMed  Google Scholar 

  51. Heinzen EL, Booth RG, Pollack GM (2005) Neuronal nitric oxide modulates morphine antinociceptive tolerance by enhancing constitutive activity of the mu-opioid receptor. Biochem Pharmacol 69:679–688

    Article  PubMed  CAS  Google Scholar 

  52. Heinzen EL, Pollack GM (2003) Pharmacokinetics and pharmacodynamics of L-arginine in rats: a model of stimulated neuronal nitric oxide synthesis. Brain Res 989:67–75

    Article  PubMed  CAS  Google Scholar 

  53. Bush MA, Pollack GM (2001) Pharmacokinetics and pharmacodynamics of 7-nitroindazole, a selective nitric oxide synthase inhibitor, in the rat hippocampus. Pharm Res 18:1607–1612

    Article  PubMed  CAS  Google Scholar 

  54. Heinzen EL, Pollack GM (2002) Use of an electrochemical nitric oxide sensor to detect neuronal nitric oxide production in conscious, unrestrained rats. J Pharmacol Toxicol Methods 48:139–146

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, USA

    Gary M. Pollack

Authors
  1. Gary M. Pollack
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary M. Pollack .

Editor information

Editors and Affiliations

  1. , Dept. of Physiology & Biochemistry, University of Malta, Biomedical Sciences Building, Msida MSD, 2080, Malta

    Giuseppe Di Giovanni

  2. Consorzio "Mario Negri" Sud, Via Nazionale, Santa Maria Imbaro, 66030, Chieti, Italy

    Vincenzo Di Matteo

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Pollack, G.M. (2013). Indirect Analysis of Nitric Oxide and Quantitation of Selective Nitric Oxide Synthase Inhibitors in Microdialysate Samples. In: Di Giovanni, G., Di Matteo, V. (eds) Microdialysis Techniques in Neuroscience. Neuromethods, vol 75. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-173-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-173-8_14

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-172-1

  • Online ISBN: 978-1-62703-173-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation