Contribution of nitric oxide to the presynaptic inhibition by endothelin ETB receptor of the canine stellate ganglionic transmission

Citation
K. Yamada et al., Contribution of nitric oxide to the presynaptic inhibition by endothelin ETB receptor of the canine stellate ganglionic transmission, J PHARM EXP, 290(3), 1999, pp. 1175-1181
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
ISSN journal
0022-3565 → ACNP
Volume
290
Issue
3
Year of publication
1999
Pages
1175 - 1181
Database
ISI
SICI code
0022-3565(199909)290:3<1175:CONOTT>2.0.ZU;2-K
Abstract
We previously reported that endothelin (ET)3 inhibited presynaptically the dog stellate ganglionic transmission. Here, we report the investigation of the possible involvement of nitric oxide pathway in the endothelin-induced inhibition of the ganglionic transmission. The amount of acetylcholine rele ased by preganglionic stimulation for 10 min was concentration-dependently inhibited after exposure to ET-3 (10(-9)-10(-6) M) or IRL-1620, endothelin ETB receptor agonist (10(-8)-10(-5) M). The inhibition was antagonized by p retreatment with a nonselective endothelin receptors antagonist (bosentan) and an ETB receptor antagonist (BQ-788) or a neuronal nitric oxide synthase inhibitor, 3-bromo-7-nitroindazole, but was not inhibited by a selective E TA receptor antagonist, BQ-123. The reduction induced by ET-3 was also anta gonized by treatment with a selective inhibitor of soluble guanylyl cyclase , 1H-[1,2,4]oxadia-zolo[4,3-a]quinoxalin-1-one. In addition, similar reduct ions were also mimicked by exposure to cGMP analog, 8-bromo-guanosine-3,5-c yclic monophosphate and nitric oxide donor, S-nitroso-N-acetylpenicillamine . Exposure to ET-3 or IRL-1620 for a 30-min period increased the levels of total nitric oxide (NO), nitrite plus nitrate NOx concentration in the incu bation medium, with the increase in NOx also being antagonized by BQ-788 at the same concentration. The ET-3-induced increase in NOx was antagonized b y treatment with the same concentration of 3-bromo-7-nitroindazole or a sel ective inhibitor of receptor-mediated Ca2+ entry, 1-[b-[3-(4-methoxyphenyl) propoxy]-4-methoxyphenethyl]-1H-imidazole (10(-5) M), and with a calmoduli n antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide. These res ults indicate that ETB receptor activation inhibits the sympathetic ganglio nic transmission via reducing acetylcholine release from presynaptic nerve terminals, although this inhibition also seems to involve the ETB receptor- operated Ca2+-calmodulin-dependent activation of endogenous nitric oxide pr oduction.