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Research ArticleArticle

Enhancement of Long-Term Potentiation by a Potent Nitric Oxide-Guanylyl Cyclase Activator, 3-(5-Hydroxymethyl-2-furyl)-1-benzyl-indazole

Wei-Lin Chien, Keng-Chen Liang, Che-Ming Teng, Sheng-Chu Kuo, Fang-Yu Lee and Wen-Mei Fu
Molecular Pharmacology June 2003, 63 (6) 1322-1328; DOI: https://doi.org/10.1124/mol.63.6.1322
Wei-Lin Chien
Pharmacological Institute, College of Medicine (W.-L.C., C-M.T., W.-M.F.) and Department of Psychology (K.-C.L.), National Taiwan University; Taipei, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan (S.-C.K., F.-Y.L.)
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Keng-Chen Liang
Pharmacological Institute, College of Medicine (W.-L.C., C-M.T., W.-M.F.) and Department of Psychology (K.-C.L.), National Taiwan University; Taipei, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan (S.-C.K., F.-Y.L.)
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Che-Ming Teng
Pharmacological Institute, College of Medicine (W.-L.C., C-M.T., W.-M.F.) and Department of Psychology (K.-C.L.), National Taiwan University; Taipei, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan (S.-C.K., F.-Y.L.)
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Sheng-Chu Kuo
Pharmacological Institute, College of Medicine (W.-L.C., C-M.T., W.-M.F.) and Department of Psychology (K.-C.L.), National Taiwan University; Taipei, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan (S.-C.K., F.-Y.L.)
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Fang-Yu Lee
Pharmacological Institute, College of Medicine (W.-L.C., C-M.T., W.-M.F.) and Department of Psychology (K.-C.L.), National Taiwan University; Taipei, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan (S.-C.K., F.-Y.L.)
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Wen-Mei Fu
Pharmacological Institute, College of Medicine (W.-L.C., C-M.T., W.-M.F.) and Department of Psychology (K.-C.L.), National Taiwan University; Taipei, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan (S.-C.K., F.-Y.L.)
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Abstract

Nitric oxide (NO) is known to affect synaptic plasticity in various regions of the brain via the cGMP–cGMP-dependent protein kinase (PKG) pathway. We found that a novel compound 3-(5-hydroxymethyl-2-furyl)-1-benzyl-indazole (YC-1), a drug known to modulate the response of soluble guanylyl cyclase to NO, greatly potentiates long-term potentiation (LTP). This compound markedly enhanced the induction of LTP in rat hippocampal and amygdala slices by weak tetanic stimulation. The potentiation of LTP by YC-1 was greatly reduced by NO synthase inhibitor Ng-nitro-l-arginine-methylester, guanylyl cyclase inhibitor 1 H-[1,2,4]-oxadiazolo(4,3-a)-quinoxalin-1-one, and PKG inhibitor (9S,10R,12R)-2,3,9,10,11,12, hexahydro-10-methoxy-2,9-dimethyl-1-ox0–9.12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-I][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT5823). In addition, mitogen-activated protein kinase kinase inhibitor 2′-amino-3′-methoxyflavone (PD98059) also markedly inhibited LTP potentiating action of YC-1. Intracellular increase of Ca2+ concentration derived from N-methyl-d-aspartate and glutamate metabotropic receptors contributes to the potentiating action of YC-1. Concurrent perfusion of YC-1 and NO donor sodium nitroprusside for a short time period resulted in the induction of LTP by stimuli at a frequency as low as 0.02 Hz. Incubation of unstimulated hippocampal slices with YC-1 plus nitroprusside increased the immunofluorescence of phospho-extracellular signal-regulated kinase (ERK) and phospho-cAMP response element binding protein (CREB). Furthermore, the Western blot shows that the phosphorylation of ERKs 1 and 2 and CREB of unstimulated hippocampal slices was increased by YC-1 plus nitroprusside, which was inhibited by KT5823. The NO-cGMP-PKG-ERK signaling pathway thus plays important role in the potentiation of LTP by YC-1.

  • Received September 30, 2002.
  • Accepted February 19, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 63 (6)
Molecular Pharmacology
Vol. 63, Issue 6
1 Jun 2003
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Research ArticleArticle

Enhancement of Long-Term Potentiation by a Potent Nitric Oxide-Guanylyl Cyclase Activator, 3-(5-Hydroxymethyl-2-furyl)-1-benzyl-indazole

Wei-Lin Chien, Keng-Chen Liang, Che-Ming Teng, Sheng-Chu Kuo, Fang-Yu Lee and Wen-Mei Fu
Molecular Pharmacology June 1, 2003, 63 (6) 1322-1328; DOI: https://doi.org/10.1124/mol.63.6.1322

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Research ArticleArticle

Enhancement of Long-Term Potentiation by a Potent Nitric Oxide-Guanylyl Cyclase Activator, 3-(5-Hydroxymethyl-2-furyl)-1-benzyl-indazole

Wei-Lin Chien, Keng-Chen Liang, Che-Ming Teng, Sheng-Chu Kuo, Fang-Yu Lee and Wen-Mei Fu
Molecular Pharmacology June 1, 2003, 63 (6) 1322-1328; DOI: https://doi.org/10.1124/mol.63.6.1322
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