Involvement of presynaptic voltage-dependent Kv3 channel in endothelin-1-induced inhibition of noradrenaline release from rat gastric sympathetic nerves

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• 作者：Kumiko Nakamura ; Takahiro Shimizu ; Kenjiro Tanaka ; Keisuke Taniuchi ; Kunihiko Yokotani
• 关键词：Endothelin-1 ; Kv channel ; Noradrenline release ; Stomach
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 出版时间：5 November, 2012
• 年：2012
• 卷：694
• 期：1-3
• 页码：98-103
• 全文大小：332 K

文摘

We previously reported that two types of K⁺ channels, the BK type Ca²⁺-activated K⁺ channel coupled with phospholipase C (PLC) and the voltage-dependent K⁺ channel (Kv channel), are, respectively, involved in the prostanoid TP receptor- and muscarinic M₂ receptor-mediated inhibition of noradrenaline (NA) release from rat gastric sympathetic nerves. In the present study, therefore, we examined whether these K⁺ channels are involved in endothelin-1-induced inhibition of NA release, using an isolated, vascularly perfused rat stomach. The gastric sympathetic postganglionic nerves around the left gastric artery were electrically stimulated twice at 2.5 Hz for 1 min, and endothelin-1 was added during the second stimulation. Endothelin-1 (1, 2 and 10 nM) dose-dependently inhibited gastric NA release. Endothelin-1 (2 nM)-induced inhibition of NA release was neither attenuated by PLC inhibitors [U-73122 (3 ¦ÌM) and ET-18-OCH₃ (3 ¦ÌM)] nor by Ca²⁺-activated K⁺ channel blockers [charybdotoxin (0.1 ¦ÌM) (a blocker of BK type K⁺ channel) and apamin (0.3 ¦ÌM) (a blocker of SK type K⁺ channel)]. The endothelin-1-induced inhibitory response was also not attenuated by ¦Á-dendrotoxin (0.1 ¦ÌM) (a selective inhibitor of Kv1 channel), but abolished by 4-aminopyridine (20 ¦ÌM) (a selectively inhibitory dose for Kv3 channel). These results suggest the involvement of a voltage-dependent Kv3 channel in the endothelin-1-induced inhibition of NA release from the gastric sympathetic nerves in rats.