| Co-Investigator(Kenkyū-buntansha) |
AKI Yasuharu Kagawa Medical University, Department of Pharmacology, Assistant, 医学部, 助手 (50231816)
KIMURA Syoji Kagawa Medical University, Department of Pharmacology, Assistant Professor, 医学部, 助教授 (30253264)
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| Research Abstract |
The "bio-sampling" technique called microdialysis was originally developed by Ungerstedt and colleagues. The principle of this method is to extract metabolizes from the extracellular fluid (ECF) without removal of fluid from the tissue. The basic device is a thin (0.65 mm diameter) double lumen probe. However, this size is relatively large for the application to the kidney or heart which is perfused at high blood flow rate. Moreover, since these organs move, the fixation of probe is difficult. In addition, to observe the rapid responses to various stimuli high dialysis efficiency will be required for probe. Thus, in order to satisfy the above points, we have tried to develop a new microdialysis probe for the kidney. The diameter of the new probe is only 0.2 mm and the dialysis efficiency is 5-10 times greater than the commercial probe. Using this newly developed probe we have performed the following experiments. 1) Intrarenal adenosine (Ado) metabolism : Ado concentration (conc.) at ba
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sal condition was around 200 nM.Ischemia increased the ado conc.about 3 times. However, after the inhibition of ado deaminase with EHNA the ado conc. was increased more than 50 times during ischemia. On the other hand, ado conc.after the inhibition of ado kinase with iodotubercidine increased only 5 times. Thus, the adenosine produced in the cell during renal ischemia might be mainly metabolized by ado deaminase and the rephosphorylation of ado might be small. 2) Effects of halothane (Hal) on the metabolism of nitric oxide (NO) in the kidney : Inhalation of Hal (2%) decreased blood pressure and the renal interstitial conc.of cyclic GMP (cGMP) and NOx, Administration of nitroprusside (NP) under the inhalation of Hal increased cGMP.These findings suggested that Hal inhibited the nitric oxide-guanylate cyclase signaling pathway in the kidney, and the renal hemodynamic responses to Hal might be induced, in part, through this inhibition. In addition, it can be assumed that the action site of Hal might be proximal to the nitric oxide-guanylate cyclase signaling pathway. Thus, the newly developed microdialysis probe is a useful tool for studying the dynamics of various substances in ECF. Less
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