1997 Fiscal Year Final Research Report Summary
Role of nitric oxide in the regulation of airway iontransport
| Project/Area Number |
08670681
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
TAMAOKI Jun Department of Medjcine, Associate Professor, 医学部, 助教授 (60147395)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Airwat epithelium / Ion transport / Nitric oxide / Cyclic AMP / Cyclic GMP / Cl channel / Airway inflammation / Asthma |
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| Research Abstract |
There is increasing evidence that nitric oxide (NO), a multipurpose messenger molecule generated from the amino acid L-arginine by nitric oxide synthase (NOS), plays a role in a variety of airway functions including vascular and airway smooth muscle tone, host defense, and pulmonary neurotransmission. In the present study, we investigated the role of NO in the regulation of airway epithelial ion tmsport function in vitro and transepithelial potential difference (PD) in vivo. Additoin of neurokinin A (NKA) and substance P (SP) increased short-circuit current of canine cultured tracheal epithelial cells in a concentratino-dependent manner, and these effects were abolished by dephenylamine carboxylate but not by amiloride. Tracheal transepithelial PD was also increased by NKA and SP.Preincubation of cells or tracheal perfusion with NG-nitro-L-arginine methylester (L-NAME,1 mM) attenuated the NKA- and SP-induced increase in short-circuit current and the amiloride-sensitive PD,causing a rightward displacement of the dose-response curves, whereas NG-nitro-D-arginine (D-NAME,1 mM) did not. The inhibitory effect of L-NAME was reversed by L-arginine (10 mM) but not by D-arginine (10 mM). The release of NO was determined by a real-time measurement of NO concentration ([NO]) in the perfusate using specific amperometric sensors for this molecule. NKA and SP increased [NO] in a dose-dependent manner. Therefore, tachykinins increase short-circuit current in vitro and amiloride-sensitive PD in vivo, which probably reflect Cl movement from the submucosa toward the respiratory lumen in tracheal mucosa and that NO generation by epithelial cells may be involved in this process.
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Research Products
(10 results)
