Bidirectional Regulation of Human Colonic Smooth Muscle Contractility by Tachykinin NK2 Receptors
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- Nakamura Akihiro
- Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan
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- Tanaka Takahiro
- Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan
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- Imanishi Akio
- Exploratory Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan
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- Kawamoto Makiko
- Exploratory Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan
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- Toyoda Masao
- Department of Surgery, Saiseikai-Nakatsu Hospital, Japan
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- Mizojiri Gaku
- Department of Surgery, Saiseikai-Nakatsu Hospital, Japan
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- Tsukimi Yasuhiro
- Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan
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In this study, we attempted to clarify the mechanism of tachykinin-induced motor response in isolated smooth muscle preparations of the human colon. Fresh specimens of normal colon were obtained from patients suffering from colonic cancer. Using mucosa-free smooth muscle strips, smooth muscle tension with circular direction was monitored isometrically. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) produced marked contraction. All of these contractions were inhibited by saredutant, a selective NK2-R antagonist, but not by CP122721, a selective NK1-R antagonist or talnetant, a selective NK3-R antagonist. βAla8-NKA(4-10) induced concentration-dependent contraction similar to NKA, but Sar9-Met11-SP and Met-Phe7-NKB did not cause marked contraction. Colonic contraction induced by βAla8-NKA(4-10) was completely blocked by saredutant, but not by atropine. Tetrodotoxin or NG-nitro-L-arginine methyl ester pretreatment significantly enhanced βAla8-NKA(4-10)–induced contraction. Immunohistochemical analysis showed that the NK2-R was expressed on the smooth muscle layers and myenteric plexus where it was also co-expressed with neuronal nitric oxide synthase in the myenteric plexus. These results suggest that the NK2-R is a major contributor to tachykinin-induced smooth muscle contraction in human colon and that the NK2-R–mediated response consists of an excitatory component via direct action on the smooth muscle and an inhibitory component possibly via nitric oxide neurons.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 117 (2), 106-115, 2011
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680155111552
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- NII論文ID
- 10029896200
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 11285990
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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