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Kazuo Kitamura - One of the best experts on this subject based on the ideXlab platform.

  • Overexpression of Proadrenomedullin N-terminal 20 peptide blunts blood pressure rise and attenuates myocardial hypertrophy and fibrosis in hypertensive rats.
    FEBS Letters, 2005
    Co-Authors: Kenji Kuwasako, Johji Kato, Yujiro Asada, Kensaku Nishihira, Kazuo Kitamura
    Abstract:

    We developed a transgenic (Tg) rat model that overexpresses human Proadrenomedullin N-terminal 20 peptide (PAMP) only and then compared the effects of unilateral nephrectomy followed by a high salt diet for five weeks in Tg and wild-type rats. We found that systolic blood pressure was significantly lower in Tg UNX rats and cardiac hypertrophy and myocardial fibrosis was also attenuated in Tg rats. Evaluation of gene expression showed suppression of cardiac local renin-angiotensin system (RAS) in Tg rat. These results suggest that in addition to reducing blood pressure, PAMP suppresses cardiac hypertrophy through negative regulation of the local cardiac RAS.

  • plasma levels of Proadrenomedullin n terminal 20 peptide and adrenomedullin in patients undergoing hemodialysis
    Nephron Clinical Practice, 2004
    Co-Authors: Takeshi Tokura, Hiroshi Kinoshita, Shouichi Fujimoto, Kazuo Kitamura
    Abstract:

    Background: Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide present in the precursor of adrenomedullin (AM), a vasodilative and natriuretic peptide. However, the profile of PAMP in hemodialyzed (HD) patients has not been determined. Methods: We measured plasma levels of PAMP, total AM (tAM) and a mature form of AM (mAM, the biologically active form) in HD patients (n = 31) and in normal controls (n = 21). Results: Plasma concentrations of PAMP before HD were significantly higher than those in controls (4.02 ± 0.24 vs. 1.64 ± 0.12 fmol/ml, p Conclusion: PAMP and AM may be involved in the regulation of blood volume in patients undergoing HD.

  • Proadrenomedullin n terminal 20 peptide pamp an endogenous anticholinergic peptide its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla
    Journal of Neurochemistry, 2002
    Co-Authors: Fumi Katoh, Kazuo Kitamura, Kenji Kangawa, Hideyuki Kobayashi, Ryuichi Yamamoto, Hiromi Niina, Hisanori Washimine, Yoshitaka Yamamoto, Akihiko Wada
    Abstract:

    In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca 2+ -dependent exocytotic cosecretion of Proadrenomedullin N-terminal 20 peptide (PAMP) (EC 50 =50.1 μM) and catecholamines (EC 50 =63.0 μM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP[1-20]NH 2 inhibited carbachol-induced 22 Na + influx via nicotinic receptors (IC 50 =2.5 μM) in a noncompetitive manner and thereby reduced carbachol-induced 45 Ca 2+ influx via voltage-dependent Ca 2+ channels (IC 50 =1.0 μM) and catecholamine secretion (IC 50 =1.6 μM). It did not alter high K + -induced 45 Ca 2+ influx via voltage-dependent Ca 2+ channels or veratridine-induced 22 Na + influx via voltage-dependent Na + channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca 2+ -dependent exocytosis in response to nicotinic receptor stimulation

  • biosynthesis and secretion of adrenomedullin and Proadrenomedullin n terminal 20 peptide in a rat model of endotoxin shock
    Hypertension Research, 2001
    Co-Authors: Eizaburo Matsui, Kazuo Kitamura, Johji Kato, Miho Yoshida, Yujiro Asada, Akinobu Sumiyoshi
    Abstract:

    To study the biosyntheses and pathophysiological roles of adrenomedullin (AM) and Proadrenomedullin N-terminal 20 peptide (PAMP) in septic shock, we compared the time course of plasma concentrations of these peptides and blood pressure in rats injected with either 0.9% saline (control group) or lipopolysaccharide (LPS group). The plasma AM concentration in the LPS group did not increase 30 and 60 min after LPS injection, at which time points the blood pressure remained low. Thereafter, AM rapidly increased, and it amounted to 35 times the basal value 4 h after injection, when the blood pressure returned to the basal level. The increment of plasma PAMP in the LPS group was lower than that of AM. We also examined the tissue concentration of AM and PAMP—as well as the tissue expression of Proadrenomedullin (proAM) mRNA—in the LPS and control groups. LPS significantly increased the tissue concentrations of AM and PAMP in the lung, but decreased them in the adrenal gland and cardiac atrium. The LPS injection augmented proAM gene transcription in the lung, adrenal gland and aorta. In an immunohistochemical examination, AM staining was intense in alveolar endothelial cells of the lung in the LPS group. Thus, this septic shock model had high plasma levels of PAMP as well as AM, while the biosynthesis and secretion of the two peptides may have been differentially regulated in various tissues of rats injected with LPS. The present results suggest that these two bioactive peptides may play different roles in the pathophysiology of septic shock.(Hypertens Res 2001; 24: 543-549)

  • secretion of Proadrenomedullin n terminal 20 peptide from cultured neonatal rat cardiac cells
    Life Sciences, 2001
    Co-Authors: Toshihiro Tsuruda, Kenji Kuwasako, Kazuo Kitamura, Johji Kato, Takuroh Imamura, Yasushi Koiwaya, Kenji Kangawa
    Abstract:

    Abstract Proadrenomedullin N-terminal 20 peptide (PAMP) is generated from post-transcriptional enzymatic processing of a 185-amino acid precursor for adrenomedullin (AM), a potent vasodilator peptide. We have reported that AM is secreted from cultured neonatal rat cardiac myocytes and fibroblasts, and that secreted AM modulates the growth of these cells; however, it is unknown whether or not the cardiac cells produce PAMP. In this study, we examined the production of PAMP in cultured neonatal rat cardiac myocytes and fibroblasts. Both the cardiac myocytes and fibroblasts cultured with serum-free media secreted PAMP time-dependently at rates of 5.7±0.9 fmol/105 cells/40 h and 8.4±0.7 fmol/5×104 cells/48 h (mean±SD), respectively. Reverse-phase high performance liquid chromatography showed that immunoreactive PAMP secreted from these cells was identical to PAMP[1-20], a whole active molecule. PAMP and AM secretions were significantly (P

Kenji Kangawa - One of the best experts on this subject based on the ideXlab platform.

  • midregional Proadrenomedullin reflects cardiac dysfunction in haemodialysis patients with cardiovascular disease
    Nephrology Dialysis Transplantation, 2007
    Co-Authors: Fumiki Yoshihara, Kenji Kangawa, Andrea Ernst, Nils G Morgenthaler, Takeshi Horio, Satoko Nakamura, Hajime Nakahama, Hiroto Nakata, Andreas Bergmann, Yuhei Kawano
    Abstract:

    BACKGROUND: Although adrenomedullin is an indicator of cardiac dysfunction in haemodialysis patients, the clinical significance of midregional Proadrenomedullin has not been elucidated. Objectives. We evaluated whether midregional Proadrenomedullin reflects cardiac dysfunction, systemic inflammation or blood volume in haemodialysis patients. METHODS: Plasma midregional Proadrenomedullin, C-reactive protein and delta body weight (indicating excessive blood volume), and two-dimensional as well as Doppler echocardiographic variables were measured just before haemodialysis in 70 patients with cardiovascular disease. RESULTS: The median value of midregional Proadrenomedullin was 1.93 nmol/l before haemodialysis, and these levels were significantly reduced following haemodialysis. Log [midregional Proadrenomedullin] was positively correlated with left ventricular end-systolic volume index, diameter of inferior vena cava, C-reactive protein and delta body weight (r = 0.328, r = 0.421, r = 0.356, r = 0.364), and negatively with blood pressure, deceleration time of an early diastolic filling wave, pulmonary venous flow velocity ratio and left ventricular ejection fraction (r = -0.330, r = -0.324, r = -0.479, r = -0.373). Multivariate regression analysis revealed that pulmonary venous flow velocity ratio, diameter of inferior vena cava and C-reactive protein were independently related factors for midregional Proadrenomedullin concentration. CONCLUSION: Plasma midregional Proadrenomedullin levels increase in association with cardiac dysfunction, systemic inflammatory status and systemic blood volume in haemodialysis patients with concomitant cardiovascular disease.

  • Midregional Proadrenomedullin reflects cardiac dysfunction in haemodialysis patients with cardiovascular disease
    Nephrology Dialysis Transplantation, 2007
    Co-Authors: Fumiki Yoshihara, Kenji Kangawa, Andrea Ernst, Nils G Morgenthaler, Takeshi Horio, Satoko Nakamura, Hajime Nakahama, Hiroto Nakata, Andreas Bergmann, Yuhei Kawano
    Abstract:

    Background. Although adrenomedullin is an indicator of cardiac dysfunction in haemodialysis patients, the clinical significance of midregional Proadrenomedullin has not been elucidated. Objectives. We evaluated whether midregional Proadrenomedullin reflects cardiac dysfunction, systemic inflammation or blood volume in haemodialysis patients. Methods. Plasma midregional Proadrenomedullin, C-reactive protein and delta body weight (indicating excessive blood volume), and two-dimensional as well as Doppler echocardiographic variables were measured just before haemodialysis in 70 patients with cardiovascular disease. Results. The median value of midregional Proadrenomedullin was 1.93 nmol/l before haemodialysis, and these levels were significantly reduced following haemodialysis. Log [midregional Proadrenomedullin] was positively correlated with left ventricular endsystolic volume index, diameter of inferior vena cava, C-reactive protein and delta body weight (r ¼ 0.328, r ¼ 0.421, r ¼ 0.356, r ¼ 0.364), and negatively with blood pressure, deceleration time of an early diastolic filling wave, pulmonary venous flow velocity ratio and left ventricular ejection fraction (r ¼� 0.330, r ¼� 0.324, r ¼� 0.479, r ¼� 0.373). Multivariate regression analysis revealed that pulmonary venous flow velocity ratio, diameter of inferior vena cava and C-reactive protein were independently related factors for midregional Proadrenomedullin concentration. Conclusion. Plasma midregional Proadrenomedullin levels increase in association with cardiac dysfunction, systemic inflammatory status and systemic blood volume in haemodialysis patients with concomitant cardiovascular disease.

  • Proadrenomedullin n terminal 20 peptide pamp an endogenous anticholinergic peptide its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla
    Journal of Neurochemistry, 2002
    Co-Authors: Fumi Katoh, Kazuo Kitamura, Kenji Kangawa, Hideyuki Kobayashi, Ryuichi Yamamoto, Hiromi Niina, Hisanori Washimine, Yoshitaka Yamamoto, Akihiko Wada
    Abstract:

    In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca 2+ -dependent exocytotic cosecretion of Proadrenomedullin N-terminal 20 peptide (PAMP) (EC 50 =50.1 μM) and catecholamines (EC 50 =63.0 μM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP[1-20]NH 2 inhibited carbachol-induced 22 Na + influx via nicotinic receptors (IC 50 =2.5 μM) in a noncompetitive manner and thereby reduced carbachol-induced 45 Ca 2+ influx via voltage-dependent Ca 2+ channels (IC 50 =1.0 μM) and catecholamine secretion (IC 50 =1.6 μM). It did not alter high K + -induced 45 Ca 2+ influx via voltage-dependent Ca 2+ channels or veratridine-induced 22 Na + influx via voltage-dependent Na + channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca 2+ -dependent exocytosis in response to nicotinic receptor stimulation

  • secretion of Proadrenomedullin n terminal 20 peptide from cultured neonatal rat cardiac cells
    Life Sciences, 2001
    Co-Authors: Toshihiro Tsuruda, Kenji Kuwasako, Kazuo Kitamura, Johji Kato, Takuroh Imamura, Yasushi Koiwaya, Kenji Kangawa
    Abstract:

    Abstract Proadrenomedullin N-terminal 20 peptide (PAMP) is generated from post-transcriptional enzymatic processing of a 185-amino acid precursor for adrenomedullin (AM), a potent vasodilator peptide. We have reported that AM is secreted from cultured neonatal rat cardiac myocytes and fibroblasts, and that secreted AM modulates the growth of these cells; however, it is unknown whether or not the cardiac cells produce PAMP. In this study, we examined the production of PAMP in cultured neonatal rat cardiac myocytes and fibroblasts. Both the cardiac myocytes and fibroblasts cultured with serum-free media secreted PAMP time-dependently at rates of 5.7±0.9 fmol/105 cells/40 h and 8.4±0.7 fmol/5×104 cells/48 h (mean±SD), respectively. Reverse-phase high performance liquid chromatography showed that immunoreactive PAMP secreted from these cells was identical to PAMP[1-20], a whole active molecule. PAMP and AM secretions were significantly (P

  • increased plasma Proadrenomedullin n terminal 20 peptide in patients with essential hypertension
    Annals of Clinical Biochemistry, 1999
    Co-Authors: Kenji Kuwasako, Kazuo Kitamura, Kenji Kangawa, Yuichiro Ishiyama, Johji Kato
    Abstract:

    The novel hypotensive peptide, Proadrenomedullin N-terminal 20 peptide (PAMP), is processed from the adrenomedullin precursor. Recently, we identified PAMP-12 [PAMP(9-20)] from the porcine adrenal medulla as a major endogenous and biologically active peptide. Using a new, sensitive radioimmunoassay which recognizes the C-terminal region of PAMP-20 [PAMP(1-20)], we investigated the role of PAMP in patients with essential hypertension who had normal renal function, and whether PAMP-12 is present in humans. The mean PAMP plasma concentration, like that of adrenomedullin, was significantly higher in hypertensive [1·51 fmol/mL, standard error of the mean (SEM) 0·09 fmol/mL] than normotensive participants (1·08 fmol/mL, SEM 0·05). The increase in plasma PAMP concentration in patients with organ damage accompanied by hypertension was significantly higher than that in patients without organ damage. The PAMP concentration had a significant positive correlation with mean blood pressure and adrenomedullin concentrat...

Nils G Morgenthaler - One of the best experts on this subject based on the ideXlab platform.

  • plasma midregional Proadrenomedullin in newborn infants impact of prematurity and perinatal infection
    Pediatric Research, 2012
    Co-Authors: D Admaty, Nils G Morgenthaler, Jorg Benzing, T Burkhardt, Olav Lapaire, L Hegi, Gabor Szinnai, H U Bucher, Christoph Buhrer, Sven Wellmann
    Abstract:

    Plasma midregional Proadrenomedullin in newborn infants: impact of prematurity and perinatal infection

  • distribution and correlates of midregional Proadrenomedullin in the general population
    Clinical Chemistry, 2009
    Co-Authors: Nils G Morgenthaler, Andreas Bergmann, Joachim Struck, Gustav J Smith, Christopher Newtoncheh, Bo Hedblad, Thomas J Wang, Olle Melander
    Abstract:

    Adrenomedullin (ADM)1 is a multifunctional peptide hormone expressed in most tissues and in multiple cell types in response to cellular stress, ischemia, and hypoxia. These characteristics indicate that ADM may have a role in protection against cellular injury and therefore is a promising biomarker of disease (1). Increased ADM concentrations have been reported in multiple diseases; however, the results between studies have been inconsistent, perhaps owing to technical difficulties in measuring ADM (2). To overcome these problems a novel assay has been developed. This assay reflects ADM production by measurement of midregional Proadrenomedullin (MR-proADM), a separate fragment of the precursor peptide preProadrenomedullin. MR-proADM, which has no known function and is produced in a 1:1 stoichiometry to ADM. The MR-proADM assay has been shown to exhibit low intraassay variability, and concentrations of MR-proADM appear stable in samples that are stored at room temperature for up to 72 h, undergo multiple freeze-thaw cycles, or are drawn from patients in a nonfasting state (2). We used the previously described immunoluminometric sandwich assay (2) (Brahms) to measure MR-proADM in 5258 fasting individuals from the cardiovascular cohort of the population-based Malmo Diet and Cancer Study who attended a baseline visit between 1991 and 1996 (3). We studied the relation of MR-proADM with 23 other baseline variables (Table …

  • homogeneous time resolved fluoroimmunoassay for the measurement of midregional Proadrenomedullin in plasma on the fully automated system b r a h m s kryptor
    Clinical Biochemistry, 2009
    Co-Authors: Pascaline Caruhel, Nils G Morgenthaler, Christian Mazier, Jan Kunde, Bruno Darbouret
    Abstract:

    Objectives Evaluate the first automated assay measuring a mid regional fragment of the Proadrenomedullin (MR-proADM). Design and methods B.R.A.H.M.S MR-proADM KRYPTOR® is a homogeneous assay. Results In 144 healthy individuals, MR-proADM mean (SD) was measured at 0.37 nmol/L (0.09). High correlation with the manual assay, B.R.A.H.M.S MR-proADM LIA, was found on 281 samples from patients suffering from community acquired pneumonia (correlation coefficient 0.97). Conclusions This fast assay can be used in low respiratory tract infections.

  • Homogeneous time-resolved fluoroimmunoassay for the measurement of midregional Proadrenomedullin in plasma on the fully automated system B.R.A.H.M.S KRYPTOR.
    Clinical biochemistry, 2009
    Co-Authors: Pascaline Caruhel, Nils G Morgenthaler, Christian Mazier, Jan Kunde, Bruno Darbouret
    Abstract:

    Evaluate the first automated assay measuring a mid regional fragment of the Proadrenomedullin (MR-proADM). B.R.A.H.M.S MR-proADM KRYPTOR is a homogeneous assay. In 144 healthy individuals, MR-proADM mean (SD) was measured at 0.37 nmol/L (0.09). High correlation with the manual assay, B.R.A.H.M.S MR-proADM LIA, was found on 281 samples from patients suffering from community acquired pneumonia (correlation coefficient 0.97). This fast assay can be used in low respiratory tract infections.

  • midregional Proadrenomedullin reflects cardiac dysfunction in haemodialysis patients with cardiovascular disease
    Nephrology Dialysis Transplantation, 2007
    Co-Authors: Fumiki Yoshihara, Kenji Kangawa, Andrea Ernst, Nils G Morgenthaler, Takeshi Horio, Satoko Nakamura, Hajime Nakahama, Hiroto Nakata, Andreas Bergmann, Yuhei Kawano
    Abstract:

    BACKGROUND: Although adrenomedullin is an indicator of cardiac dysfunction in haemodialysis patients, the clinical significance of midregional Proadrenomedullin has not been elucidated. Objectives. We evaluated whether midregional Proadrenomedullin reflects cardiac dysfunction, systemic inflammation or blood volume in haemodialysis patients. METHODS: Plasma midregional Proadrenomedullin, C-reactive protein and delta body weight (indicating excessive blood volume), and two-dimensional as well as Doppler echocardiographic variables were measured just before haemodialysis in 70 patients with cardiovascular disease. RESULTS: The median value of midregional Proadrenomedullin was 1.93 nmol/l before haemodialysis, and these levels were significantly reduced following haemodialysis. Log [midregional Proadrenomedullin] was positively correlated with left ventricular end-systolic volume index, diameter of inferior vena cava, C-reactive protein and delta body weight (r = 0.328, r = 0.421, r = 0.356, r = 0.364), and negatively with blood pressure, deceleration time of an early diastolic filling wave, pulmonary venous flow velocity ratio and left ventricular ejection fraction (r = -0.330, r = -0.324, r = -0.479, r = -0.373). Multivariate regression analysis revealed that pulmonary venous flow velocity ratio, diameter of inferior vena cava and C-reactive protein were independently related factors for midregional Proadrenomedullin concentration. CONCLUSION: Plasma midregional Proadrenomedullin levels increase in association with cardiac dysfunction, systemic inflammatory status and systemic blood volume in haemodialysis patients with concomitant cardiovascular disease.

Akihiko Wada - One of the best experts on this subject based on the ideXlab platform.

  • Expression of adrenomedullin and Proadrenomedullin N-terminal 20 peptide in PC12 cells after exposure to nerve growth factor
    Neuroscience, 2020
    Co-Authors: Hideyuki Kobayashi, Toshihiko Yanagita, Hiroki Yokoo, S Itoh, Takashi Sugano, Akihiko Wada
    Abstract:

    Adrenomedullin (AM) and Proadrenomedullin N-terminal 20 peptide (PAMP) are multi-functional peptides derived from the same precursor, Proadrenomedullin. We have studied the regulatory mechanism of expression of these peptides during neuronal differentiation of rat pheochromocytoma PC12 cells by nerve growth factor (NGF). The cellular levels of the peptides increased slightly, and then progressively decreased below the control by NGF. Immunoreactive (ir)-AM in the medium was transiently increased by NGF. Cytochemical staining showed that ir-AM and ir-PAMP were abundantly present in cytoplasm in the undifferentiated cells, and were decreased during culture with NGF. There was no preferential localization of ir-AM or ir-PAMP in neurites in comparison with in cytoplasm in the differentiated cells. Northern blot analysis showed that mRNA encoding these peptides, as detected as a band of 1.6 kb, increased more than three-fold at 1 h after the addition of NGF and then progressively decreased to one fifth of the control during 72 h. Degradation rate of the mRNA was slowed by NGF even when mRNA level is decreased after 72 h of NGF treatment. The transcription rate of their gene increased transiently and then decreased by the long-term treatment with NGF. These results demonstrate that expression of AM and PAMP is regulated by NGF along with time-dependent differentiation: AM gene transcription is transiently activated by NGF, whereas it was suppressed during neuronal differentiation of the cells.

  • Proadrenomedullin n terminal 20 peptide pamp an endogenous anticholinergic peptide its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla
    Journal of Neurochemistry, 2002
    Co-Authors: Fumi Katoh, Kazuo Kitamura, Kenji Kangawa, Hideyuki Kobayashi, Ryuichi Yamamoto, Hiromi Niina, Hisanori Washimine, Yoshitaka Yamamoto, Akihiko Wada
    Abstract:

    In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca 2+ -dependent exocytotic cosecretion of Proadrenomedullin N-terminal 20 peptide (PAMP) (EC 50 =50.1 μM) and catecholamines (EC 50 =63.0 μM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP[1-20]NH 2 inhibited carbachol-induced 22 Na + influx via nicotinic receptors (IC 50 =2.5 μM) in a noncompetitive manner and thereby reduced carbachol-induced 45 Ca 2+ influx via voltage-dependent Ca 2+ channels (IC 50 =1.0 μM) and catecholamine secretion (IC 50 =1.6 μM). It did not alter high K + -induced 45 Ca 2+ influx via voltage-dependent Ca 2+ channels or veratridine-induced 22 Na + influx via voltage-dependent Na + channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca 2+ -dependent exocytosis in response to nicotinic receptor stimulation

  • Adrenomedullin and Proadrenomedullin N-terminal 20 peptide (PAMP) in adrenal chromaffin cells
    Peptides, 2001
    Co-Authors: Hideyuki Kobayashi, Toshihiko Yanagita, Hiroki Yokoo, Akihiko Wada
    Abstract:

    Abstract Adrenomedullin (AM) and Proadrenomedullin N-terminal 20 peptide (PAMP) are peptides having multiple physiological functions and are most abundantly expressed in the adrenal medulla. In addition to PAMP, PAMP12, a 12 amino acid peptide with sequence identity to PAMP between amino acids 9–20, has also been shown to be expressed in the adrenal medulla. AM, PAMP and PAMP12 are released along with catecholamines by regulated exocytosis upon stimulation of adrenal chromaffin cells. PAMP and PAMP12 regulate catecholamine release and synthesis by interfering with nicotinic cholinergic receptors in these chromaffin cells. AM may also cause gradual release of catecholamine from these cells. AM, PAMP and PAMP12 are endogenous peptides that modulate chromaffin cell function via different mechanisms.

  • Selective inhibition of nicotinic cholinergic receptors by Proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells.
    Molecular Brain Research, 2001
    Co-Authors: Hideyuki Kobayashi, Kenji Kuwasako, Kazuo Kitamura, Ryuichi Yamamoto, Shin-ichi Minami, Toshihiko Yanagita, Seiji Shiraishi, Hiroki Yokoo, Akihiko Wada
    Abstract:

    Abstract We studied whether a novel Proadrenomedullin derived peptide was present and what was its physiological function in cultured bovine adrenal chromaffin cells. We found a high level of Proadrenomedullin N-terminal 12 peptide (PAMP-12) which consists of a peptide from 9th amino acid to 20th amino acid of Proadrenomedullin N-terminal 20 peptide (PAMP-20). PAMP-12 was released from the cells along with catecholamine upon stimulation of nicotinic cholinergic receptors. When PAMP-12 was added in the incubation medium, this peptide inhibited nicotinic receptor-mediated catecholamine release and influx of Na+ and Ca2+ into the cells. PAMP-12 did not affect catecholamine release evoked by histamine or by depolarization by high concentration of potassium. PAMP-12 also inhibited synthesis of catecholamines as well as the activation of tyrosine hydroxylase by nicotinic stimulation. Thus, PAMP-12 is an endogenous peptide that regulates release and synthesis of catecholamines by acting on nicotinic cholinergic receptors in an autocrine manner in adrenal chromaffin cells.

  • cyclic amp dependent synthesis and release of adrenomedullin and Proadrenomedullin n terminal 20 peptide in cultured bovine adrenal chromaffin cells
    FEBS Journal, 1999
    Co-Authors: Hideyuki Kobayashi, Kazuo Kitamura, Ryuichi Yamamoto, Shin-ichi Minami, Toshihiko Yanagita, Hiromi Niina, Keizo Masumoto, Futoshi Izumi, Dominique Aunis, Akihiko Wada
    Abstract:

    Adrenomedullin and Proadrenomedullin N-terminal 20 peptide are peptides with multiple physiological functions and are most abundant in adrenal medulla. We studied whether the cAMP-dependent pathway is involved in the regulation of synthesis and release of adrenomedullin and Proadrenomedullin N-terminal 20 peptide in cultured bovine adrenal chromaffin cells. Exposure of the cells to dibutyryl cAMP (dbcAMP) increased a progressive accumulation of immunoreactive-adrenomedullin and immunoreactive-Proadrenomedullin N-terminal 20 peptide in the extracellular medium, while reciprocally decreasing their cellular content in a time-dependent manner. The decrease of levels of both peptides in the cells was much greater in extent than the increase of the peptides in the medium. H89, an inhibitor of cAMP-dependent protein kinase attenuated these changes, induced by dbcAMP. The resulting changes by dbcAMP and H89 were similar to those of chromogranin B, a marker peptide of chromaffin granule. Northern blot analysis showed that the mRNA encoding these peptides, detected as a band of 1.6 kb, was decreased by the treatment with dbcAMP. The effect of dbcAMP on mRNA was attenuated by H89, and was reversible as the decreased mRNA level caused by dbcAMP could be returned to control levels by culturing cells after removal of dbcAMP. These results suggest that the cAMP-dependent protein kinase pathway stimulates the release of adrenomedullin and Proadrenomedullin N-terminal 20 peptide, whereas it lowers synthesis of these peptides via the reduction of their transcript level.

Andreas Bergmann - One of the best experts on this subject based on the ideXlab platform.

  • distribution and correlates of midregional Proadrenomedullin in the general population
    Clinical Chemistry, 2009
    Co-Authors: Nils G Morgenthaler, Andreas Bergmann, Joachim Struck, Gustav J Smith, Christopher Newtoncheh, Bo Hedblad, Thomas J Wang, Olle Melander
    Abstract:

    Adrenomedullin (ADM)1 is a multifunctional peptide hormone expressed in most tissues and in multiple cell types in response to cellular stress, ischemia, and hypoxia. These characteristics indicate that ADM may have a role in protection against cellular injury and therefore is a promising biomarker of disease (1). Increased ADM concentrations have been reported in multiple diseases; however, the results between studies have been inconsistent, perhaps owing to technical difficulties in measuring ADM (2). To overcome these problems a novel assay has been developed. This assay reflects ADM production by measurement of midregional Proadrenomedullin (MR-proADM), a separate fragment of the precursor peptide preProadrenomedullin. MR-proADM, which has no known function and is produced in a 1:1 stoichiometry to ADM. The MR-proADM assay has been shown to exhibit low intraassay variability, and concentrations of MR-proADM appear stable in samples that are stored at room temperature for up to 72 h, undergo multiple freeze-thaw cycles, or are drawn from patients in a nonfasting state (2). We used the previously described immunoluminometric sandwich assay (2) (Brahms) to measure MR-proADM in 5258 fasting individuals from the cardiovascular cohort of the population-based Malmo Diet and Cancer Study who attended a baseline visit between 1991 and 1996 (3). We studied the relation of MR-proADM with 23 other baseline variables (Table …

  • midregional Proadrenomedullin reflects cardiac dysfunction in haemodialysis patients with cardiovascular disease
    Nephrology Dialysis Transplantation, 2007
    Co-Authors: Fumiki Yoshihara, Kenji Kangawa, Andrea Ernst, Nils G Morgenthaler, Takeshi Horio, Satoko Nakamura, Hajime Nakahama, Hiroto Nakata, Andreas Bergmann, Yuhei Kawano
    Abstract:

    BACKGROUND: Although adrenomedullin is an indicator of cardiac dysfunction in haemodialysis patients, the clinical significance of midregional Proadrenomedullin has not been elucidated. Objectives. We evaluated whether midregional Proadrenomedullin reflects cardiac dysfunction, systemic inflammation or blood volume in haemodialysis patients. METHODS: Plasma midregional Proadrenomedullin, C-reactive protein and delta body weight (indicating excessive blood volume), and two-dimensional as well as Doppler echocardiographic variables were measured just before haemodialysis in 70 patients with cardiovascular disease. RESULTS: The median value of midregional Proadrenomedullin was 1.93 nmol/l before haemodialysis, and these levels were significantly reduced following haemodialysis. Log [midregional Proadrenomedullin] was positively correlated with left ventricular end-systolic volume index, diameter of inferior vena cava, C-reactive protein and delta body weight (r = 0.328, r = 0.421, r = 0.356, r = 0.364), and negatively with blood pressure, deceleration time of an early diastolic filling wave, pulmonary venous flow velocity ratio and left ventricular ejection fraction (r = -0.330, r = -0.324, r = -0.479, r = -0.373). Multivariate regression analysis revealed that pulmonary venous flow velocity ratio, diameter of inferior vena cava and C-reactive protein were independently related factors for midregional Proadrenomedullin concentration. CONCLUSION: Plasma midregional Proadrenomedullin levels increase in association with cardiac dysfunction, systemic inflammatory status and systemic blood volume in haemodialysis patients with concomitant cardiovascular disease.

  • Midregional Proadrenomedullin reflects cardiac dysfunction in haemodialysis patients with cardiovascular disease
    Nephrology Dialysis Transplantation, 2007
    Co-Authors: Fumiki Yoshihara, Kenji Kangawa, Andrea Ernst, Nils G Morgenthaler, Takeshi Horio, Satoko Nakamura, Hajime Nakahama, Hiroto Nakata, Andreas Bergmann, Yuhei Kawano
    Abstract:

    Background. Although adrenomedullin is an indicator of cardiac dysfunction in haemodialysis patients, the clinical significance of midregional Proadrenomedullin has not been elucidated. Objectives. We evaluated whether midregional Proadrenomedullin reflects cardiac dysfunction, systemic inflammation or blood volume in haemodialysis patients. Methods. Plasma midregional Proadrenomedullin, C-reactive protein and delta body weight (indicating excessive blood volume), and two-dimensional as well as Doppler echocardiographic variables were measured just before haemodialysis in 70 patients with cardiovascular disease. Results. The median value of midregional Proadrenomedullin was 1.93 nmol/l before haemodialysis, and these levels were significantly reduced following haemodialysis. Log [midregional Proadrenomedullin] was positively correlated with left ventricular endsystolic volume index, diameter of inferior vena cava, C-reactive protein and delta body weight (r ¼ 0.328, r ¼ 0.421, r ¼ 0.356, r ¼ 0.364), and negatively with blood pressure, deceleration time of an early diastolic filling wave, pulmonary venous flow velocity ratio and left ventricular ejection fraction (r ¼� 0.330, r ¼� 0.324, r ¼� 0.479, r ¼� 0.373). Multivariate regression analysis revealed that pulmonary venous flow velocity ratio, diameter of inferior vena cava and C-reactive protein were independently related factors for midregional Proadrenomedullin concentration. Conclusion. Plasma midregional Proadrenomedullin levels increase in association with cardiac dysfunction, systemic inflammatory status and systemic blood volume in haemodialysis patients with concomitant cardiovascular disease.

  • measurement of midregional Proadrenomedullin in plasma with an immunoluminometric assay
    Clinical Chemistry, 2005
    Co-Authors: Nils G Morgenthaler, Joachim Struck, Christine Alonso, Andreas Bergmann
    Abstract:

    Background: Adrenomedullin (ADM) is a potent vasodilatory peptide, and circulating concentrations have been described for several disease states, including dysfunction of the cardiovascular system and sepsis. Reliable quantification has been hampered by the short half-life, the existence of a binding protein, and physical properties. Here we report the technical evaluation of an assay for midregional pro-ADM (MR-proADM) that does not have these problems. Methods: MR-proADM was measured in a sandwich immunoluminometric assay using 2 polyclonal antibodies to amino acids 45–92 of proADM. The reference interval was defined in EDTA plasma of 264 healthy individuals (117 male, 147 female), and increased MR-proADM concentrations were found in 95 patients with sepsis and 54 patients with cardiovascular disease. Results: The assay has an analytical detection limit of 0.08 nmol/L, and the interassay CV was 0.12 nmol/L. The assay was linear on dilution with undisturbed recovery of the analyte. EDTA-, heparin-, and citrate-plasma samples were stable (<20% loss of analyte) for at least 3 days at room temperature, 14 days at 4 °C, and 1 year at −20 °C. MR-proADM values followed a gaussian distribution in healthy individuals with a mean (SD) of 0.33 (0.07) nmol/L (range, 0.10–0.64 nmol/L), without significant difference between males or females. The correlation coefficient for MR-proADM vs age was 0.50 ( P <0.001). MR-proADM was significantly ( P <0.001) increased in patients with cardiovascular disease [median (range), 0.56 (0.08–3.9) nmol/L] and patients with sepsis [3.7 (0.72–25.4) nmol/L]. Conclusions: MR-proADM is stable in plasma of healthy individuals and patients. MR-proADM measurements may be useful for evaluating patients with sepsis, systemic inflammation, or heart failure.