title: Involvement of nitric oxide pathways in short term modulation of tyrosine hydroxylase activity by endothelins 1 and 3 in the rat anterior hypothalamus.
abstract: The ability of endothelins 1 and 3 (ET-1 and ET-3) to reduce neuronal norepinephrine release through ETB receptor activation involving nitric oxide (NO) pathways in the rat anterior hypothalamus region (AHR) was previously reported. In the present work, we studied the effects of ET-1 and -3 on tyrosine hydroxylase (TH) activity and the possible involvement of NO pathways. Results showed that ET-1 and -3 (10 nM) diminished TH activity in AHR and this effect was blocked by a selective ETB receptor antagonist (100 nM BQ-788), but not by a ET(A) receptor antagonist (BQ-610). To confirm these results, 1 microM IRL-1620 (ET(B) agonist) reduced TH activity whereas 300 nM sarafotoxin S6b falled to modify it. N(omega)-Nitro-L-arginine methyl ester (10 microM), 7-nitroindazole (10 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-ona (10 microM), KT5823 (2 microM), inhibitors of nitric oxide synthase, neuronal nitric oxide synthase, NO-sensitive-guanylyl cyclase, and protein kinase G, respectively, did not modify the reduction of TH activity produced by ETs. In addition, both 100 microM sodium nitroprusside and 50 microM 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and guanosine-3',5'-cyclic monophosphate analog, respectively) diminished TH activity. Present results showed that ET-1 and ET-3 diminished TH activity through the activation of ET(B) receptors involving the NO/guanosine-3',5'-cyclic monophosphate/protein kinase G pathway. Taken jointly present and previous results it can be concluded that both ETs play an important role as modulators of norepinephrine neurotransmission in the rat AHR.
authors: Cátedra de Fisiología e Instituto de Química y Metabolismo del Fármaco (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors: Carolina
authors: C
authors: Morgazo
authors: Guadalupe
authors: G
authors: Perfume
authors: Guillermina
authors: G
authors: Legaz
authors: Andrea
authors: A
authors: di Nunzio
authors: Sandra I
authors: SI
authors: Hope
authors: Liliana G
authors: LG
authors: Bianciotti
authors: Marcelo S
authors: MS
authors: Vatta
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D019334:Endothelin-3 / Q000502:physiology*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000502:physiology*; D007191:Indazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D013498:Suramin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D002227:Carbazoles; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D007191:Indazoles; D007211:Indoles; D009842:Oligopeptides; D010069:Oxadiazoles; D010880:Piperidines; D011810:Quinoxalines; C073601:KT 5823; C087220:BQ 610; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C086539:BQ 788; D013498:Suramin; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D006152:Cyclic GMP; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester