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Amino Acids

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Synthesis of homoagmatine and GC–MS analysis of tissue homoagmatine and agmatine: evidence that homoagmatine but not agmatine is a metabolite of pharmacological L-homoarginine in the anesthetized rat

  • Dimitrios TsikasEmail author
  • Alexander Bollenbach
  • Erik Hanff
  • Bibiana Beckmann
  • Björn Redfors
Original Article

Abstract

Low L-homoarginine (hArg) concentrations in human blood and urine are associated with renal and cardiovascular morbidity and mortality, yet the underlying mechanisms and the biological activities of hArg are elusive. In humans and rats, hArg is metabolized to l-lysine. The aim of the present work was to study hArg metabolism to agmatine (Agm) and homoagmatine (hAgm) in the anesthetized rat. Using a newly developed and validated GC–MS method and a newly synthesized and structurally characterized hAgm we investigated the metabolism of i.p. administered hArg (0, 20, 220, 440 mg/kg) to hAgm and Agm in lung, kidney, liver and heart in anesthetized rats. Our study provides unequivocal evidence that hArg is metabolized to hAgm but not to Agm. Whether hAgm derived from hArg’s metabolism may contribute to the pathophysiological significance of endogenous hArg and for the favoured effects of pharmacological hArg remains to be demonstrated. The biology of hArg warrants further investigations.

Keywords

AGAT Amino acids GC–MS Organs Polyamines 

Abbreviations

ADC

l-Arginine decarboxylase

AGAT

l-Arginine:glycine amidinotransferase

Agm

Agmatine

AGMA

Agmatinase

GC–MS

Gas chromatography–mass spectrometry

hAgm

Homoagmatine

hArg

L-Homoarginine

i.p

Intraperitoneal

LLOQ

Lower limit of quantitation (LLOQ)

m/z

Mass-to-charge ratio

NO

Nitric oxide synthase

NOS

Nitric oxide

ODC

l-Ornithine decarboxylase

PAR

Peak area ratio

PFP

Pentafluoropropionyl

PFPA

Pentafluoropropionic anhydride

PUT

Putrescine

SIM

Selected-ion monitoring

SPD

Spermidine

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical statement

Rats received humane care and the study protocol complied with the institutional guidelines of the Sahlgrenska University Hospital.

Supplementary material

726_2019_2808_MOESM1_ESM.pdf (562 kb)
Supplementary material 1 (PDF 561 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Toxicology, Core Unit Proteomics, Core Unit ProteomicsHannover Medical SchoolHannoverGermany
  2. 2.Institute of Occupational MedicineHannover Medical SchoolHannoverGermany
  3. 3.Department of CardiologySahlgrenska University HospitalGothenburgSweden

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