Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca2+ channel activity via imidazoline I2 receptor activation

Young Hwan Kim, Ji Hyun Jeong, Duck Sun Ahn, Seungsoo Chung

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca2+ channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca2+ influx through N-type Ca2+ channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca2+ current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca2+ channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension.

Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number3
DOIs
StatePublished - Aug 26 2016
Externally publishedYes

Keywords

  • Agmatine
  • Imidazoline receptor
  • N-type calcium channel
  • Sympathetic tone

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