The methylester of γ-butyrobetaine, but not γ-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation

Maija Dambrova, Stefan Chlopicki, Edgars Liepinsh, Olga Kirjanova, Olga Gorshkova, Valery I. Kozlovski, Staffan Uhlen, Inta Liepina, Ramona Petrovska, Ivars Kalvinsh

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Gamma-butyrobetaine (GBB) is known mostly as a bio-precursor of carnitine, a key molecule in the regulation of myocardial energy metabolism. The metabolites of carnitine and GBB were investigated for acetylcholine-like activity decades ago. The present study shows that the methylester of GBB (GBB-ME) exerts its biological activity by binding to muscarinic acetylcholine receptors. GBB-ME dose-dependently decreased the blood pressure in anaesthetised rats and also produced endothelium-dependent vasodilation in the isolated guinea-pig heart. The biological effects of GBB-ME were inhibited partially by the NOS inhibitor Nω-nitro-L-arginine methyl-ester (L-NAME) and abolished by the acetylcholine receptor antagonist atropine, thus supporting the hypothesis that GBB-ME acts as muscarinic agonist. Moreover, we have shown here for the first time that GBB-ME binds directly to transfected human muscarinic (m) acetylcholine receptors, the potency order being m2>m5≥m4≥m1>m3. GBB itself showed neither biological activity nor significant affinity for the m1-5 receptors. We conclude that GBB-ME, but not the parent GBB, possesses acetylcholine-like activity in vivo and in vitro.

Original languageEnglish
Pages (from-to)533-539
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume369
Issue number5
DOIs
Publication statusPublished - May 2004
Externally publishedYes

Keywords

  • Blood pressure
  • Gamma-butyrobetaine
  • Methyl ester
  • Muscarinic acetylcholine receptor

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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