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Dambrova, M. et al.

Dambrova, Chlopicki, Liepinsh, Kirjanova, Gorshkova, Kozlovski, Uhlen, Liepina, Petrovska, Kalvinsh,

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

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 N(omega)-nitro-L-arginine methylester (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> or =m4> or =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.[1]

References

The methylester of gamma-butyrobetaine, but not gamma-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation. Dambrova, M., Chlopicki, S., Liepinsh, E., Kirjanova, O., Gorshkova, O., Kozlovski, V.I., Uhlen, S., Liepina, I., Petrovska, R., Kalvinsh, I. Naunyn Schmiedebergs Arch. Pharmacol. (2004) [Pubmed]

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