Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation

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 u...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2016-08, Vol.477 (3), p.406-412
Main Authors: Kim, Young-Hwan, Jeong, Ji-Hyun, Ahn, Duck-Sun, Chung, Seungsoo
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Agmatine - pharmacology
Animals
Calcium Channel Blockers - pharmacology
Calcium Channels, N-Type - drug effects
Electric Stimulation
Imidazoline Receptors - agonists
In Vitro Techniques
Male
Mesenteric Arteries - drug effects
Rats
Rats, Sprague-Dawley
Sympathetic Nervous System - drug effects
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Summary: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 Ca(2+) 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 Ca(2+) influx through N-type Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
ISSN:1090-2104
DOI:10.1016/j.bbrc.2016.06.086