論文 - 北村 和雄
-
Shimokubo T., Sakata J., Kitamura K., Kangawa K., Matsuo H., Eto T.
Life Sciences 57 ( 19 ) 1771 - 1779 1995年9月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Life Sciences
Adrenomedullin is a strong vasorelaxing peptide discovered in pheochromocytoma tissue. Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to cause pulmonary hypertension. To test the hypothesis that adrenomedullin plays a role similar to that of atrial natriuretic peptide or brain natriuretic peptide in modulating right ventricular responses to pulmonary hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of monocrotaline treated rats with those of control rats. We also measured the effect of pulmonary hypertension on plasma level of the peptide. The concentrations of adrenomedullin immunoreactivity in right ventricle and plasma were significantly higher in monocrotaline treated rats than in control rats. The messenger RNA level of adrenomedullin in right ventricle was also higher in monocrotaline treated rats than in control rats. These results suggest that adrenomedullin participates in the mechanism to counteract the high blood pressure in pulmonary circulation. © 1995.
-
Shimosawa T., Ito Y., Ando K., Kitamura K., Kangawa K., Fujita T.
Journal of Clinical Investigation 96 ( 3 ) 1672 - 1676 1995年9月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Investigation
Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin, which are derived from proadrenomedullin, exhibit remarkable hypotensive action. We investigated the effect of PAMP and adrenomedullin on peripheral sympathetic neural transmission. Using perfused rat mesenteric arteries, PAMP (0, 1, 5, and 10 pmol/ml) decreased norepinephrine overflow by periarterial electrical nerve stimulation in a dose-dependent fashion (0.244 ± 0,043, 0,231 ± 0.048, 0.195 ± 0.061, and 0.168 ± 0.051 ng/gram tissue weight: NS, P < 0.05, and P < 0.02, respectively). In contrast to PAMP, adrenomedullin (1, 5, and 10 pmol/ml) did not change it. In contrast, vasoconstrictive response of mesenteric arteries to exogenous norepinephrine was significantly attenuated by 10 pmol/ml of adrenomedullin but not by the same dose of PAMP. Calcitonin gene-related peptide (8-37) [CGRP(8-37)], a CGRP receptor antagonist, inhibited the vasodilatory effect of adrenomedullin but could not suppress the sympathoinhibitory effect of PAMP. Neither a nicotinic antagonist, hexamethonium, nor a presynaptic α2 antagonist, yohimbine, blocked the sympathoinhibitory effect of PAMP. Thus, it suggests that PAMP and adrenomedullin, which are derived from the same gene, exhibit different hypotensive mechanisms: PAMP inhibits neural transmission at peripheral sympathetic nerve ending, although adrenomedullin directly dilates vascular smooth muscle, possibly through CGRP-like receptor.
DOI： 10.1172/JCI118208
-
HAEMODYNAMIC RESPONSES TO RAT ADRENOMEDULLIN IN ANAESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS 査読あり
Ishiyama Y., Kitamura K., Ichiki Y., Sakata J., Kida O., Kangawa K., Eto T.
Clinical and Experimental Pharmacology and Physiology 22 ( 9 ) 614 - 618 1995年9月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical and Experimental Pharmacology and Physiology
1. The haemodynamic effects of rat adrenomedullin (AM), a novel hypotensive peptide, were examined in anaesthetized 16–18 week old spontaneously hypertensive rats (SHR) and Wistar‐Kyoto rats (WKY). 2. An intravenous injection of rat AM dose‐dependently reduced the mean blood pressure (MBP) with a concomitant fall in total peripheral resistance index (TPRI) and an increase in cardiac index (CI) in both strains of rats. Per cent changes in MBP, TPRI and CI were not different between SHR and WKY. 3. The plasma half‐life of rat AM in SHR was similar to that in WKY when it was administered at the dose of 1.0 nmol/kg. 4. These findings indicate that AM has a potent vasorelaxant activity in both SHR and WKY. The haemodynamic responsiveness to exogenous AM and its pharmaeokinetics in SHR were comparable with those in WKY. Copyright © 1995, Wiley Blackwell. All rights reserved
-
Receptors for adrenomedullin in human vascular endothelial cells 査読あり
Kato J., Kitamura K., Kangawa K., Eto T.
European Journal of Pharmacology: Molecular Pharmacology 289 ( 2 ) 383 - 385 1995年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：European Journal of Pharmacology: Molecular Pharmacology
Accumulation of the intracellular cyclic AMP (cAMP) was measured in cultured endothelial cells of the human umbilical vein following the incubation with adrenomedullin, a newly discovered hypotensive peptide, to determine the presence of specific receptors for adrenomedullin. Adrenomedullin increased the intracellular cAMP in a dose-dependent fashion in the endothelial cells, and the EC50 value was as low as 10-9 M. Calcitonin gene-related peptide (CGRP) that has a homology to adrenomedullin in its amino-acid sequence also increased the intracellular cAMP with an EC50 value greater than 10-7 M. The effect of CGRP was attenuated in the presence of CGRP-(8-37) had no effect on the cAMP accumulation by adrenomedullin. These findings indicate that the cultured endothelial cells of human umbilical vein possess specific adrenomedullin receptors coupled with the adenylate cyclase activity that may have little affinity with CGRP. © 1995.
-
Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue 査読あり
Washimine H., Asada Y., Kitamura K., Ichiki Y., Hara S., Yamamoto Y., Kangawa K., Sumiyoshi A., Eto T.
Histochemistry and Cell Biology 103 ( 4 ) 251 - 254 1995年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Histochemistry and Cell Biology
The histological localization was investigated of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma. The immunohistological distribution was examined of AM in human, rat, and procine tissues using a polyclonal antibody to a fragment comprising C-terminal amino acids 40-52 of human adrenomedullin [AM(40-52)NH2]. Almost all of the human pheochromocytoma and normal adrenal medullary cells of all three species were immunostained and found to be intensely positive for AM. Furthermore, AM-immunoreactive cells were present in the pancreatic islets, gastrointestinal neuroendocrine system, anterior pituitary, and choroid plexus with some degree of interspecies heterogeneity. These findings indicate that AM-immunoreactive cells are widely distributed in the endocrine and neuroendocrine system, suggesting that AM plays some important role in the control of systemic and local circulation and also of humoral secretion. © 1995 Springer-Verlag.
DOI： 10.1007/BF01457408
-
Mechanisms of adrenomedullin-induced vasodilation in the rat kidney 査読あり
Hirata Y., Hayakawa H., Suzuki Y., Suzuki E., Ikenouchi H., Kohmoto O., Kimura K., Kitamura K., Eto T., Kangawa K., Matsuo H., Omata M.
Hypertension 25 ( 4 II ) 790 - 795 1995年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Hypertension
To explore the mechanism of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: -29±2% [SEM]; P<.01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P<.05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P<.05). Adrenomedullin decreased renal vascular resistance (10-7 mol/L adrenomedullin: -41 ± 2%; P<.001) and increased release of nitric oxide (+5.1±0.7 fmol/min per gram kidney weight; P<.001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor N(G)- monomethyl-L-arginine, and it also reversed the decrease in renal vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10-7 mol/L adrenomedullin: +0.8±0.2 fmol/min per gram kidney weight; P<.01 versus control) and renal vasodilation (-28±6%; P<.05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P<.05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.
-
Molecular forms of human brain natriuretic peptide (BNP) in plasma of patients on hemodialysis (HD) 査読あり
Y Ishizaka 1, Y Yamamoto, M Tanaka, F Kato, Y Ishizaka, N Yokota, J Kato, K Kitamura, T Eto, K Kangawa, et al.
Clin Nephrol . 1995 Apr;43(4):237-42. 43 ( 4 ) 237 - 242 1995年4月
掲載種別：研究論文（学術雑誌）
-
Adrenomedullin: Implications for Hypertension Research 査読あり
Kitamura K., Kangawa K., Matsuo H., Eto T.
Drugs 49 ( 4 ) 485 - 495 1995年4月
-
Shimekake Y., Nagata K., Ohta S., Kambayashi Y., Teraoka H., Kitamura K., Eto T., Kangawa K., Matsuo H.
Journal of Biological Chemistry 270 ( 9 ) 4412 - 4417 1995年3月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Biological Chemistry
The biological action of adrenomedullin, a novel hypotensive peptide, on bovine aortic endothelial cells, was examined. The specific binding of adrenomedullin to these cells was observed, and adrenomedullin was found to induce intracellular cAMP accumulation in a dose-dependent manner. EC50 for the cAMP accumulation was about 100 times lower than the apparent IC50 for the binding assay. Adrenomedullin also induced increase of intracellular free Ca2+ in endothelial cells in a dose-dependent manner. The Ca2+ response to adrenomedullin was biphasic with an initial transient increase due to the release from thapsigargin-sensitive intracellular Ca2+ storage and a prolonged increase by influx through the ion channel on the plasma membrane. This intracellular free Ca2+ increase resulted from phospholipase C activation and inositol 1,4,5-trisphosphate formation, and seemed to cause nitric oxide synthase activation by monitoring intracellular cGMP accumulation. Both cAMP accumulation and Ca2+ increased responses to adrenomedullin were mediated by cholera toxin-sensitive G protein, but the two signal transduction pathways were independent. Thus, the results suggest that adrenomedullin elicits the hypotensive effect through at least two mechanisms, a direct action on vascular smooth muscle cells to increase intracellular cAMP and an action on endothelial cells to stimulate nitric oxide release, with both leading to vascular relaxation.
-
Katoh F., Kitamura K., Niina H., Yamamoto R., Washimine H., Kangawa K., Yamamoto Y., Kobayashi H., Eto T., Wada A.
Journal of Neurochemistry 64 ( 1 ) 459 - 461 1995年1月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Neurochemistry
Abstract: In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca2+‐dependent exocytotic cosecretion of proadrenomedullin N‐terminal 20 peptide (PAMP) (EC50 = 50.1 µM) and catecholamines (EC50 = 63.0 µM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP[1–20]NH2 inhibited carbachol‐induced 22Na+ influx via nicotinic receptors (IC50 = 2.5 µM) in a noncompetitive manner and thereby reduced carbachol‐induced 45Ca2+ influx via voltage‐dependent Ca2+ channels (IC50 = 1.0 µM) and catecholamine secretion (IC50 = 1.6 µM). It did not alter high K+‐induced 45Ca2+ influx via voltage‐dependent Ca2+ channels or veratridine‐induced 22Na+ influx via voltage‐dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca2+‐dependent exocytosis in response to nicotinic receptor stimulation. Copyright © 1995, Wiley Blackwell. All rights reserved
-
アドレノメデュリン含有細胞がラット視床下部室傍核および視索上核に存在する 査読あり
上田陽一、西野枝子、椛島成利、澁谷泉、北村和雄、寒川賢治、山下博
日本内分泌学会雑誌 71 ( 6 ) 929 - 929 1995年
掲載種別：研究論文（学術雑誌）
-
培養血管内皮細胞におけるアドレノメデュリン(AM)の産生・分泌とその調節機構 査読あり
庄司浩気、南野直人、諏合伸、北村和雄、江藤胤尚、寒川賢治、松尾壽之
日本内分泌学会雑誌 71 ( 3 ) 361 - 361 1995年
掲載種別：研究論文（学術雑誌）
-
ブタ各組織におけるアドレノメヂュリン免疫活性の分子型の同定 査読あり
市来能成、北村和雄、寒川賢治、江藤胤尚
日本内分泌学会雑誌 71 ( 3 ) 424 - 424 1995年
掲載種別：研究論文（学術雑誌）
-
起立負荷時における血中アドレノメデュリン分泌動態 査読あり
井手野順一、本多一文、中村友厚、六角久美子、斎藤孝子、北村和雄
日本 71 ( 3 ) 500 - 500 1995年
掲載種別：研究論文（学術雑誌）
-
視索上核神経内分泌細胞におけるアドレノメデュリンの作用：スライスパッチ法による検討 査読あり
椛島成利,nurhadiibrahim,澁谷泉、野口淳、上田陽一、北村和雄、寒川賢治、山下博
日本内分泌学会雑誌 71 ( 6 ) 930 - 930 1995年
掲載種別：研究論文（学術雑誌）
-
新しい循環調節因子の発見 査読あり
寒川賢治、南野直人、松尾壽之、北村和雄、江藤胤尚
日本内分泌学会雑誌 71 ( 3 ) 260 - 260 1995年
掲載種別：研究論文（学術雑誌）
-
Tanaka M., Kitamura K., Ishizaka Y., Ishiyama Y., Kato J., Eto T., Kangawa K.
Internal Medicine 34 ( 8 ) 728 - 733 1995年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
Adrenomedullin is a novel hypotensive peptide recently discovered in human pheochromocytoma. In the present study, we measured the plasma immunoreactive adrenomedullin of healthy subjects and patients with various diseases. Immunoreactive adrenomedullin was found to circulate in blood of the healthy subjects at a considerable concentration (3.3±0.3 fmol/ml). Plasma adrenomedullin was significantly increased in the patients with congestive heart failure (5.4±0.3 fmol/ml), essential hypertension (5.3±0.4 fmol/ml) and renal disease (4.9±0.4 fniol/ml). In healthy volunteers physical exercise significantly increased the plasma adrenomedullin concentration. The increase of adrenomedullin was inversely related to systolic blood pressure. These findings indicate that adrenomedullin participates in the circulation control in both physiological and diseased conditions. Although the exact origin of circulating adrenomedullin is still unknown, it is thought to be released rapidly by acute exercise, thereby regulating the cardiovascular system by its vasodilating activity. (Internal Medicine 34: 728-733, 1995). © 1995, The Japanese Society of Internal Medicine. All rights reserved.
-
視索上核神経内分泌細胞におけるアドレノメデュリンの作用：Ca2+画像解析法による検討 査読あり
椛島成利、nurtiadiIbrahim、澁谷泉、野口淳、上田陽一、北村和雄、寒川賢治、山下博
日本内分泌学会雑誌 71 ( 6 ) 930 - 930 1995年
掲載種別：研究論文（学術雑誌）
-
新しい降圧ペプチド"proadrenomedullin N-terminal 20 peptide(PAMP)"の研究:単離・構造決定, 生体内分布と生物学的活性の検討 査読あり
北村和雄、鷲峯久紀、市来能成、加藤ふみ、江藤胤尚、和田明彦、寒川賢治、松尾壽之
日本内分泌学会雑誌 71 ( 3 ) 412 - 412 1995年
担当区分：筆頭著者 掲載種別：研究論文（学術雑誌）
-
新しい降圧ペプチド“アドレノメデュリン” 査読あり
北村和雄
医学のあゆみ 173 ( 11 ) 910 - 911 1995年
担当区分：筆頭著者 掲載種別：研究論文（学術雑誌）