title: Phospholipase C-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate underlies agmatine-induced suppression of N-type Ca2+channel in rat celiac ganglion neurons.
abstract: Agmatine suppresses peripheral sympathetic tone by modulating Cav2.2 channels in peripheral sympathetic neurons. However, the detailed cellular signaling mechanism underlying the agmatine-induced Cav2.2 inhibition remains unclear. Therefore, in the present study, we investigated the electrophysiological mechanism for the agmatine-induced inhibition of Cav2.2 current (ICav2.2) in rat celiac ganglion (CG) neurons. Consistent with previous reports, agmatine inhibited ICav2.2in a VI manner. The agmatine-induced inhibition of the ICav2.2current was also almost completely hindered by the blockade of the imidazoline I2receptor (IR2), and an IR2agonist mimicked the inhibitory effect of agmatine on ICav2.2, implying involvement of IR2. The agmatine-induced ICav2.2inhibition was significantly hampered by the blockade of G protein or phospholipase C (PLC), but not by the pretreatment with pertussis toxin. In addition, diC8-phosphatidylinositol 4,5-bisphosphate (PIP2) dialysis nearly completely hampered agmatine-induced inhibition, which became irreversible when PIP2resynthesis was blocked. These results suggest that in rat peripheral sympathetic neurons, agmatine-induced IR2activation suppresses Cav2.2 channel voltage-independently, and that the PLC-dependent PIP2hydrolysis is responsible for the agmatine-induced suppression of the Cav2.2 channel.
authors.affiliation: Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Duck-Sun
authors.initials: DS
authors.lastname: Ahn
authors.affiliation: Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: sschung@yuhs.ac.
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Chung
mesh_terms: D000005:Abdomen; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D019269:Phosphatidylinositol 4,5-Diphosphate; D000376:Agmatine; D010738:Type C Phospholipases
keywords: Agmatine; Cav2.2; Imidazoline receptor; Phosphatidylinositol 4,5-bisphosphate