title: Involvement of presynaptic voltage-dependent Kv3 channel in endothelin-1-induced inhibition of noradrenaline release from rat gastric sympathetic nerves.
abstract: We previously reported that two types of K(+) channels, the BK type Ca(2+)-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 M(2) 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 μM) and ET-18-OCH(3) (3 μM)] nor by Ca(2+)-activated K(+) channel blockers [charybdotoxin (0.1 μM) (a blocker of BK type K(+) channel) and apamin (0.3 μM) (a blocker of SK type K(+) channel)]. The endothelin-1-induced inhibitory response was also not attenuated by α-dendrotoxin (0.1 μM) (a selective inhibitor of Kv1 channel), but abolished by 4-aminopyridine (20 μM) (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.
authors.affiliation: Department of Pharmacology, School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-kumiko@kochi-u.ac.jp
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokotani
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001481:Basal Metabolism / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051670:Shaw Potassium Channels / Q000378:metabolism*; D013270:Stomach / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013569:Synapses
chemical_list: D004546:Elapid Venoms; D019332:Endothelin-1; D004963:Estrenes; D010742:Phospholipid Ethers; D011760:Pyrrolidinones; D051670:Shaw Potassium Channels; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D018999:Charybdotoxin; C026659:edelfosine; D001030:Apamin; C020273:dendrotoxin; D015761:4-Aminopyridine; D009638:Norepinephrine