体液の自動調節機構に関する研究ー特に腎臓とホルモンの関与を中心に

1990 年度 実績報告書

• 研究課題/領域番号: 02304055
• 研究機関: 東京医科歯科大学
• 研究代表者: 丸茂 文昭 東京医科歯科大学, 医学部, 教授 (00050443)
• 研究分担者: 乾 賢一 東京医科歯科大学, 薬剤部, 教授 (70034030) ; 猿田 享男 慶應義塾大学, 内科学, 教授 (70051571) ; 田島 陽太郎 秋田大学, 第二生化学, 教授 (30049796) ; 斉藤 寿一 自治医科大学, 内分泌病・腎臓病学, 教授 (10048994) ; 今井 正 自治医科大学, 薬理学, 教授 (40049010)
• キーワード: 体液調節 / 腎 / 内分泌 / 高血圧 / 利尿

研究概要

本年度は、体液の自動調節機構に関する研究として特に基礎的研究を重点として行った。in vitroの実験系で今井は、単離尿細管潅流法を用いてウサギ腎接合尿細管のCa輸送に対する副甲状腺ホルモンの作用を明らかにした。田島は腎に存在するアルドステロン受容体と糖質コルチコイド受容体の性質を明らかにした。斎藤はラット腎乳頭部集合管細胞を培養し、抗利尿ホルモンの作用発現における細胞内遊離Ca濃度の役割を検討した。また、遠藤はラット腎近位尿細管に対する抗利尿ホルモンの新しい作用を見い出した。これらはいずれも、腎の電解質調節に対するホルモンの関与についての基礎的検討である。
in vitroの実験として、折田はラット腎の虚血後再潅流を行い解糖系酵素の変動を分子生物学的手法で追求した。猿田は無麻酔無拘束犬を用いてエンドセリン、EDRFなどの腎血流量に対する影響をみた。丸茂は腎炎患者における心房性Na利尿ホルモンを測定し、腎機能が血中当該ホルモン濃度と有意の関係にないことを明らかにした。これらは腎の水・電解質代謝に対するホルモンの作用を動物またはヒトのレベルで検討を試みたものである。黒川・乾・平田らもそれぞれの研究を行い、業績の項に示すような報告を行っている。このように本研究班は着実に目標に向けて進展していると言えよう。

研究成果

• [文献書誌] Ujiie,K,Nonoguchi,H,Tomita,K,Marumo,F.: "Effects of ANF on cGMP synthesis" Am.J.Physiol. 259. F535-F538 (1990)
• [文献書誌] Satoh,K,Masuda,T,Masaki,Y,Hasegawa,N,Tsuyusaki,T,Ando,K,Marumo,F,Kikawada,R.: "The Role of the Left Ventricle in Atrial Natriuretic Peptide Secretion in Acute Mitral Regulation" American Journal of Hypertension. 3. 704-706 (1990)
• [文献書誌] Marumo,F,Sakamoto,H,Ando,K,Ishigami,T.: "Concentrations of Atrial Natriuretic Peptide in Plasma and Urine of Kidney Disease Patients" Clinical Chemistry. 36. 1650-1653 (1990)
• [文献書誌] Sakamoto,H,Sasaki,S,Hirata,Y,Imai,T,Ando,K,Ida,T,Sakurai,T,Yanagisawa,M,Masaki,T,Marumo,F.: "Production of Endothelinー1 By Rat Cultured Mesangial Cells" Biochem Biophys ResーComm. 169. 462-468 (1990)
• [文献書誌] Tomita,K,Nonoguchi,H,Marumo,F.: "Effects of Endothelin on Peptideーdependent Cyclic Adenosine Monophosphate Accumulation along the Nephron Segments of the Rat" J.Clin.Invest.85. 2014-2018 (1990)
• [文献書誌] Hirata,Y.et al.: "Receptor binding and vasoconstrictor activity of big endothelin" Eur.J.Pharmacol.176. 225-228 (1990)
• [文献書誌] Hirata,Y.et al.: "Interaction of endothelin isopeptides with vascular endothelinー1 receptor" Bio med Res.11. 195-198 (1990)
• [文献書誌] Emori,T.et al.: "Specific receptor for endothelinー3 in cultured bovine endotheli al cells and its cellular mechanism of action" FEBS Lett.263. 261-264 (1990)
• [文献書誌] Hirata,Y.et al.: "Presence of endothelinー1ーlike immunoreactivity in human cerebrospinal fluid" Biochem.Biophys.Res.Commun.166. 1274-1278 (1990)
• [文献書誌] Shichiri,M.et al.: "Plasma endothelin levels in hypertension and Chronic renal failure" Hypertension. 15. 493-496 (1990)
• [文献書誌] Ohta,K.et al.: "Cytokineーinduced release of endothelinー1 from porcine renal epithelial cell line" Biochem.Biophys.Res.Commun.169. 578-584 (1990)
• [文献書誌] Fukuhara Y,Yamamoto S,Yano F,Orita Y,Fujiwara Y,Ueda N,Kamada Y,Noguchi T,Tanaka T.: "The changes in activities and mRNA levels of glycolytic enzymes of ischemiaーreperfused rat kidney." Contribution to Nephrology.
• [文献書誌] Fujiwara Y,Ochi S,Fukuhara Y,Yokoyama K,Fukunaga M,Shin S,Orita Y,Ueda N,Kamada T.: "Isotopic measurement of glomerular intracapillary volume as a quantitative index for mesangial cell contractility." Contribution to Nephrology.
• [文献書誌] Horio M,Kakihara M,Nakahama H,Orita Y,Fujiwara Y,Fukuhara Y,Ueda N,Kamada T,: "Kidney derived cells show multidrug secretory transport." Handler JS,Pastan I.Contribution to Nephrology.
• [文献書誌] T.Okuda,I,Kojima,K.Kurokawa: "Ambient CIーions modify rat mesangial cell contraction by modulating cell ionsitol triphosphate and Ca^<2+> via ehanced prostaglandin E2" J.Clin.Invest.84. 1866-1872 (1989)
• [文献書誌] K.Kurokawa,T.Okuda: "Calcium activated chloride conductance of mesangial cells" Kidney International. 38. S48-S50 (1990)
• [文献書誌] M.Fukagawa,R.Okazaki,K.Takano,S.Kaname,E.Ogata,M.Kitaoka,S.Harada,N.Sekine,T.Mitsutomo,K.Kurokawa: "Regression of parathyroid hyperplasia by calcitriolーpulse therapy in patients on longーterm dialysis" New Engl.J.Med.323. 421-422 (1990)
• [文献書誌] M.Fukagawa,S.Kaname,T.Igarashi,E.Ogata,K.Kurokawa: "Regulation of parathyroid hormonesynthesis in chronic renal failure in rats" Kidney International.
• [文献書誌] Takemoto.F,Miyanoshita.A,Shimamura.K,Sunano.S,Endou.H.: "Intranephron PGE_2 production in strokeーprone spontaneously hypertensive rats." Am.J.Physiol.258. H987-H993 (1990)
• [文献書誌] Jung,K.Y.Endou,H.: "Cellular Adenosine Triphosphate Production and Consumption in the Descending Thin Limb of Henle's Loop in the Rat." Renal Physiol.Biochem.13. 248-258 (1990)
• [文献書誌] Imai,M.,Yasoshima,K.,Yoshitomi,K.: "Mechanism of water transport across the upper portion of the descending thin limb of long looped nephron of hamsters." Pfluegers Arch. 415. 630-637 (1990)
• [文献書誌] Imai,M.,Yoshitomi,K.: "Electrophysiololgical study of inner medullary collecting duct of hamsters." Pfluegers Arch. 416. 180-188 (1990)
• [文献書誌] Matsushima,Y.,Yoshitomi,K.,Koseki,C.,Imai,M.,Akabane,S.,Kawamura,M.: "Basolateral Na/H excahnge in the hamster inner medullary collecting duct." New York Acad Sci.574. 396-398 (1989)
• [文献書誌] Matsushima,Y.,Yoshitomi,K.,Koseki,C.,Kawamura,M.Akabane,S.,Imai,M.: "Mechanisms of intracellullar pH regulation in the hamster inner medullary collecting duct perfused in vitro" Pfluegers Arch. 416. 715-721 (1990)
• [文献書誌] Shimizu,T.,Yoshitomi,K.,Nakamura,M.,Imai,M.: "Effect of parathyroid hormone on the connecting tubule from the rabbit kidney:biphasic response of transmural voltage" Pfluegers Arch. 416. 254-261 (1990)
• [文献書誌] Shimizu,T.,Yoshitomi,Y.,Nakamura,M.,Imai,M.: "Effects of PTH,calcitonin,and cAMP on calcium transport in rabbit distal nephron segments." Am J Physiol. 38. F408-414 (1990)
• [文献書誌] Itoh,H.,Toyoshima,I.,Mizunuma,H.,Kobayashi,Tashima,Y.: "Threeーstep purification method and characterization of the bovine brain 90ーkDa Heat Shock Protein." Arch.Biochem.Biophys.282. 290-296 (1990)
• [文献書誌] Matsubara,O.,Kasuga,T,Marumo,F.,Itoh,H.,Tashima,Y.: "Localization of 90ーkDa Heat Shock Protein in the kidney." Kidney Int.38. 830-834 (1990)
• [文献書誌] Nakamoto,et al.: "Effects of endothelin on systomic and renal haemodynamic and neuroendocrine hormones in conscious dogs." Clinical Science. 77. 567-572 (1989)
• [文献書誌] Murakami,et al.: "Calcitonin geneーrelated peptide modulates adrenal hormones in conscious dogs." Acta Endocrinologica.
• [文献書誌] Nakamoto,et al.: "Defferent effects of lowーand highーdoses of endothelin on hemodynamics and hormones in the normotensive conscious dogs." Journal of Hypertension.
• [文献書誌] Nakahama H,Moriyama T,Horio M,Fukuhara Y,Ueda N,Orita Y,Kamada T.: "Netilmicin affects Naーdependent Dーglucose transport and the membrane fluidity of rabbit reanl brushーborder membrane vesicles:a comparison with gentamicin." Toxicology Letter. 53. 201-202 (1990)
• [文献書誌] Ishikawa S,Saito T,Okuda K,Nagasaka S,Kuzuya T.: "Prompt recovery of plasma arginine vasopressin in diabetic coma after the therapy of intravenous infusion of a small dose of insulin and a large amount of fluid" Acta Endocrinol.122. 455-461 (1990)
• [文献書誌] Ishikawa S,Saito T.: "Agumentation of forskolinーinduced cAMP prodiction by ouabain in rat renal papillary collecting cells in culture" Biochem Biophys Res Comm. 166. 411-416 (1990)
• [文献書誌] Ishikawa S,Okuda K,Saio T.: "Prompt inhibition of arginine vasopressinーinduced cellular cAMP production by extracellular sodium depletion in rat renal inner medullary collecting duct cells in culture" Endocrinology. 127. 560-566 (1990)
• [文献書誌] Ishikawa S,Saito T: "Vasopressinーinduced increases in cellular free calcium concentration measured in single cells of rat renal papillary collecting tubule." Endocrinol Jap. 37. 381-387 (1990)
• [文献書誌] Ishikawa S,Saito T.: "Optimal concentration of cellular free calcium for AVPーinduced cAMP in collecting tubules" Kidney Int.37. 1060-1066 (1990)
• [文献書誌] T.Okuno,H.Maegawa,K.Inui,R.Hori.: "Intraction of ofloxacin with organic cation transport system in rat renal brushーborder membranes" J.Pharmacol.Exp.Ther.,. 255. 1033-1037 (1990)
• [文献書誌] Jung.K.Y.Endou.H.: "Furosemide Acts on short Loop of Descending Thin Limb,But Not on Long Loop" J.Pharmacol Exp.Ther.253. 1184-1188 (1990)
• [文献書誌] Satoh.T,Endou.H.: "Inhibitory effect of Phorbol ester on sodium transport in frog urinary baladder" Am.J.Physiol.259. F425-F431 (1990)
• [文献書誌] Jung.K.Y.,Endou.H.: "Mercury chloride as a possible phos pholipase C activator:Effect on antiotensin IIーinduced(Ca)transient in the rat early proximal tubule." Biophys.Res.Commun.173. 606-613 (1990)
• [文献書誌] Ishikawa S,Saito T.: "Inhibition by phorbol ester of cellular cAMP production and cellular free calcium mobilization in response to arginine vasopressin in rat renal papillary collecting tubule cells in culture" Endocrinology.
• [文献書誌] Okuda K,Ishikawa S,: "Interaction between endothelinーinduced Na^+ and Ca^<2+> kinetics in cultured rat vascular smooth muscle cells" J.Cardiovasc Pharmacol.
• [文献書誌] Okuda K,Ishikawa S,Saito T.: "Effect of vasopressin on Na kinetics in cultured rat vascular smooth muscle cells" Biochem Biophys Res Comm.173. 224-230 (1990)
• [文献書誌] Emori,T.et al.: "Endothelinー3 stimulates production of endotheliumーderived nitric oxide via phosphoinositide break down" Biochem.Biophys.Res.Commun.174. 228-235 (1990)
• [文献書誌] Sakamoto,H.et al.: "Production of endothelinー1 by cultured rat mesangial cells" Biochem.Biophys.Res.Commun.169. 462-468 (1990)
• [文献書誌] Togashi,K.et al.: "Abundance of endothelinー3 in human cerebrespinal fluid" Biomed Res.11. 243-246 (1990)
• [文献書誌] Kanno,K.et al.: "Endothelinー1 and vasculitis" J.A.M.A.264. 2868 (1990)
• [文献書誌] Kanno,K.et al.: "Endothelin and Raynaud's phenominon" Am.J.Med.90. 130-132 (1991)
• [文献書誌] Ando,K.et al.: "Presence of endothelinー1ーlike Immunoreactivity in human urine" Nephron. 57. 36-39 (1991)
• [文献書誌] Hirata,Y.: "The Frontiers in Nephrology" Excerpta Medica, 254 (1990)