Nitrergic Inhibition of Tachykininergic Neuro-Muscular Transmission via Cyclic GMP in the Hamster Ileum
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概要
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The present study was designed to explore the inhibitory mechanism by nitric oxide (NO) of the tachykininergic neuro-muscular transmissions in the hamster ileum. In the presence of guanethidine (1 μM), atropine (0.5 μM), nifedipine (0.1 μM) and apamin (100 nM), electrical field stimuli (EFS; 0.5 msec duration, 15 V) evoked non-adrenergic, non-cholinergic excitatory junction potentials (EJPs) in circular smooth muscle cells. The EJPs were markedly inhibited by the tachykinin NK1 receptor antagonists [D-Pro4, D-Trp7,9]-SP(4–11) (3 μM). Both the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 200 μM) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM), did not affect on the resting membrane potentials, but enhanced the tachykininergic EJPs. In the presence of L-NAME (200 μM), exogenously applied NO (10 μM) and the membrane permeable analogue of guanosine 3:5-cyclic monophosphate (cGMP), 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP, 3 mM), significantly inhibited the tachykininergic EJPs. Application of EFS (0.5 msec duration, 15 V) with trains of 20 pulses at 20 Hz increased amount of released substance P (SP). The release of SP was further increased by the treatment of L-NAME or ODQ, but markedly reduced by exogenously applied NO and 8-Br-cGMP. These results suggest that the endogenous NO may inhibit the tachykininergic neuro-muscular transmissions by the decrease of SP release from the tachykininergic neurons, possibly through a guanylate cyclase-cGMP-dependent mechanism in the hamster ileum.
著者
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MATSUYAMA Hayato
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biologi
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UNNO Toshihiro
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biologi
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KOMORI Seiichi
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biologi
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Komori Seiichi
Department Of Pathogenetic Veterinary Science The United Graduate School Of Veterinary Sciences Gifu
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Komori S
Gifu Univ. Gifu Jpn
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Unno T
Gifu Univ. Gifu Jpn
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Komori Seiichi
Laboratory Of Pharmacology Department Of Veterinary Medicine Faculty Of Agriculture United Graduate
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Matsuyama Hayato
Laboratory Of Pharmacology Department Of Veterinary Medicine Faculty Of Applied Biological Science G
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Unno Toshihiro
Laboratory Of Pharmacology Department Of Veterinary Medicine Faculty Of Agriculture United Graduate
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TAKEWAKI Tadashi
Laboratory of Physiology, Department of Basic Veterinary Science, The United Graduate School of Vete
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Takewaki Tadashi
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University
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UNNO Toshihiro
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University
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Matsuyama Hayato
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University
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