Contribution of nitric oxide to the presynaptic inhibition by endothelin ETB receptor of the canine stellate ganglionic transmission.
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 released by preganglionic stimulation for 10 min was concentration-dependently inhibited after exposure to ET-3 (10(-9)-10(-6) M) or IRL-1620, endothelin ET(B) receptor agonist (10(-8)-10(-5) M). The inhibition was antagonized by pretreatment with a nonselective endothelin receptors antagonist (bosentan) and an ET(B) receptor antagonist (BQ-788) or a neuronal nitric oxide synthase inhibitor, 3-bromo-7-nitroindazole, but was not inhibited by a selective ET(A) receptor antagonist, BQ-123. The reduction induced by ET-3 was also antagonized by treatment with a selective inhibitor of soluble guanylyl cyclase, 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one. In addition, similar reductions were also mimicked by exposure to cGMP analog, 8-bromoguanosine-3, 5-cyclic 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 NO(x) concentration in the incubation medium, with the increase in NO(x) also being antagonized by BQ-788 at the same concentration. The ET-3-induced increase in NO(x) was antagonized by treatment with the same concentration of 3-bromo-7-nitroindazole or a selective inhibitor of receptor-mediated Ca(2+) entry, 1-[b-[3-(4-methoxyphenyl) propoxy]-4-methoxyphenethyl]-1H-imidazole (10(-5) M), and with a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide. These results indicate that ET(B) receptor activation inhibits the sympathetic ganglionic transmission via reducing acetylcholine release from presynaptic nerve terminals, although this inhibition also seems to involve the ET(B) receptor-operated Ca(2+)-calmodulin-dependent activation of endogenous nitric oxide production.
Yamada
K
K
Department of Pharmacology, School of Medicine, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Kushiku
K
K
Yamada
H
H
Katsuragi
T
T
Furukawa
T
T
Noguchi
H
H
Ono
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D009842:Oligopeptides / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists; D013233:Stellate Ganglion / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D007191:Indazoles; D009842:Oligopeptides; D010069:Oxadiazoles; D010880:Piperidines; D011810:Quinoxalines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013449:Sulfonamides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; C086539:BQ 788; C017967:W 7; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D000109:Acetylcholine; C080122:7-nitroindazole