1993 Fiscal Year Final Research Report Summary
Studies on intracellular signal transduction mechanism in renal tubular cells.
| Project/Area Number |
03454123
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General physiology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
FUJIMOTO Mamoru Osaka Medical College, School of Medicine, Professor, 医学部, 教授 (70084803)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOKAWA Manabu Osaka Medical College, School of Medicine, Instructor, 医学部, 助手 (70153327)
KOTERA Kunihiko Osaka Medical College, School of Medicine, Associate Professor, 医学部, 助教授 (00084905)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Angiotensin II / Catecholamine / Tubular Na transport / cyclic AMP / Urinary acidification / Ion channel / Intracellular pH / Intracellular Ca |
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| Research Abstract |
To investigate the intracellular mechanism of signal transduction for the action of neural and humoral control in the renal proximal tubule, we employed two electrophysiological techniques., The one was direct micropuncture of ion-selective microelectrodes into in vivo bullfrog tubular cells with or without a combined use of fluorescent dye to analyze cellular ion concentrations in bullfrog kindney, and the other was the patch-clamp techniques applied to cultured opossum kidney (OK) cells of proximal tubular origin to analyze the ion channel activities in vitro. The micropuncture data showed that physiological concentration of angiotensin II(10^<-11>-10^<-12> M) cnhanced 1)acidification of proximal tubular urine by stimulating luminal Na^+/H^+ exchange mechanism, and 2)Na^+ and water reabsorption by increasing luminal permeability to Na^+. These two effects were associatedwith the suppression of cellular cyclic AMP via alpha_2 receptor mechanism. The higher concentration of angiotensin II (>10^<-10> M) caused an increment of intracellular Ca^<2+> by extra-stimulation of alpha_1 mechanism, resulting in a suppression of Na^+ and water reabsorption. The fluorescent dye technique with Acridine Orange was useful to detect the change of subcellular vesicles more strongly stained red color with the increased level of intracellular cyclic AMP, which indicates the accumulation of H^+ within the vesicle. Noradrenaline and dopamine caused acceleration and inhibition of Na^+ reasorption and H^+ secretion in the proximal tubule, depending on the level of cyclic AMP via stimulation or inhibition of alpha_2 receptor mechanism, respectively. In patch clamp studies, we found that both K^+ and C1 channel were activated when cells were imposed on hyposmotic stress. The pH-sensitive K^+ channels (70 pS), Ca^<2+> -activated K^+ channels (30 pS), pH-sensitive C1 cha
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Research Products
(20 results)
