Angiotensin-Forming Enzyme in Brain Tissue

Ganten, Detlev; Minnich, J.; Granger, Pierre; Hayduk, K; Brecht, H. M.; Barbeau, A.; Boucher, R.; Genest, Jacques

doi:10.1126/science.173.3991.64

Cited by 291 publications

(95 citation statements)

References 18 publications

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“…The presence of renin-like activity in tissues other than kidney has been reported by various authors (Carretero, Bujak & Houle, 1971;Ganten et al, 1971;Gross et al, 1964;Skeggs, Lentz, Kahn, Dorer & Levine, 1969). Among these tissues, is the submaxillary gland of the mouse (Werle et al, 1957).…”

Section: Discussionmentioning

confidence: 89%

Renin‐like activity of the rat submaxillary gland: characterization and the effect of several drugs and stimuli

Gutman¹,

Levy²,

Shorr³

1973

British J Pharmacology

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Summary1. Renin-like activity was found in rat submaxillary glands. 2. This activity was destroyed by boiling, was non-dialyzable and showed an optimum at approximately 500 C. 3. Renin-like activity in the submaxillary gland was not diminished 24 h after nephrectomy but was considerably reduced after ligature of the submaxillary duct. 4. Renin-like activity in the submaxillary gland was reduced following fooddeprivation, water-deprivation or hypovolemia. 5. Renin-like activity in the rat submaxillary gland was increased after isoproterenol administration but not following pilocarpine. 6. Renin-like activity in the rat submaxillary gland was increased considerably by administration of NaCl or KCI, as well as following adrenalectomy. 7. Chlorothiazide and ouabain increased submaxillary renin-like activity but diazoxide did not affect this activity.

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Section: Discussionmentioning

confidence: 89%

Renin‐like activity of the rat submaxillary gland: characterization and the effect of several drugs and stimuli

Gutman¹,

Levy²,

Shorr³

1973

British J Pharmacology

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“…The octapeptide ANG-II (molecular weight 1,046) is the strongest physiological vasoconstrictor known. From a large protein precursor (pre-proangiotensinogen) synthesized in the liver it is liberated in a series of proteolytic steps catalyzed by enzymes from various tissues [1][2][3]. ANG-II is very short-lived in the plasma: Once generated from ANG-I, it is degraded further into physiologically inactive peptides by various plasma peptidases, at a plasma half life of less than a minute [4].…”

Section: Introductionmentioning

confidence: 99%

Method Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry for Angiotensin-II in Human Plasma: Application to Study Interaction Between Atorvastatin & Olmesartan Drug Combination

Pal

2014

Ind J Clin Biochem

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Simple and sensitive Liquid ChromatographyTandem Mass Spectrometry (LCMS/MS) method was developed and validated, then was implicated on hypertensive human subjects to study drug interaction of atorvastatin (ATVS) and Olmesartan (OLM) on status of Angiotensin-II (ANG-II). The ANG-II in plasma was extracted with 5 mL methanol containing 5 % formic acid through C 18 (cartridges) liquid-liquid extraction, dried and reconstituted with 1 mL of 16 % acetonitrile in 0.1 % formic acid in water. The chromatographic separation of ANG-II with a Agilent technology 6410 Triple quadrupole was carried multiple reaction monitoring scan mode with a Agilent 1290 Infinity LC system for UHPLC. The sample were separated on a (Thermo Scientific) Hy-Purity advance (50 9 4.6 mm, 5 lm) using Mobile Phase A: 16 % acetonitrile in 0.1 % formic acid in water and Mobile Phase B: 0.1 % formic acid in methanol at a flow rate of 0.3 mL/min, performed at ambient temperature. The mobile phase gradient of 16 % acetonitrile in water was linearly increased to 38 % acetonitrile over 10 min and subsequently the mobile-phase was increased to 100 % acetonitrile over 15 min. The developed method was validated for specificity, accuracy, precision, stability, linearity, sensitivity and recovery. The method was linear between peak area ratio of standard and internal standard over the range of 50-800 ng/mL. The method was successfully applied for the drug interaction study revealed levels of ANG-II were significantly higher in ATV-S ? OLM treatment condition as compared to individual treatment of OLM. This reflects the reason of low effectiveness of ATVS ? OLM in combination instead of synergistic activity.

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“…Since its founding, 25 years have passed and the MDC has performed even beyond Detlev Ganten's expectations. Of course, since his first two publications appeared in Nature [1] and in Science [2], he probably believes that such publications are easy, as they were for him.…”

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confidence: 99%

A visionary scientist selects clinicians for clinical research

Luft

2016

J Mol Med

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We celebrate Detlev Ganten's 75th birthday late this March (Fig. 1); we hope he is celebrating too. Detlev Ganten is not only founding editor of the Journal of Molecular Medicine and still active in this capacity, he is also the initial director of the Max-Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. The MDC traces its heritage to the KaiserWilhelm Institute für Hirnforschung, officially founded 1931. The collaboration between Nikolai TimofejewRessovsky, Karl Zimmer, and Max Delbrück that resulted in placing genetics on a molecular footing has been told many times. When the institute was reconstituted after German reunification, Detlev Ganten was given the task of resurrecting the MDC to world-class. And so he did; for 13 years, he was at the helm. Since its founding, 25 years have passed and the MDC has performed even beyond Detlev Ganten's expectations. Of course, since his first two publications appeared in Nature [1] and in Science [2], he probably believes that such publications are easy, as they were for him.Detlev Ganten gave the MDC a unique mission, namely pursuing the highest caliber of disease-oriented (clinical) biological research focusing on the basic mechanisms and molecules of relevance in health and disease and emphasizing the most advanced methodologies in cell biology, genetics, and genomics. He was less interested in the topic and wisely supported the idea that the MDC should pursue a broad spectrum of problems comprising the current chronic scourges, namely cardiovascular disease, cancer, and neurodegenerative disorders. Similarly circumspect, the MDC has maintained this broad base until the present day.Another unique decision Detlev Ganten made was to include clinicians in the field of MDC senior scientists. As the institute had a tradition of encompassing clinical departments since the time of Oskar and Cécile Vogt, the decision was made easier. The institute had continued that tradition and before German reunification had worked intensively with a clinic dedicated to cancer and a clinic for cardiovascular diseases in the framework of the BAcademy of the Sciences^. However, although the clinics were still there, the framework was gone and to continue the concept in conjunction with the two medical schools Berlin had in 1991 was difficult. Furthermore, the mission Detlev Ganten espoused was not necessarily commensurate with the usual department chairmanships in academic medicine. Clinical excellence, teaching, and research were the appropriate criteria of the time; however, Detlev Ganten wanted the order and emphasis revised and reversed. Research at an internationally competitive level was to receive priority, yet the clinical departments also had to work; the patient care had to be excellent, and the teaching mission was not to be ignored. He found his clinicians and the search also underscores the value of personal relationships when making personnel decisions.

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Angiotensin-Forming Enzyme in Brain Tissue

Cited by 291 publications

References 18 publications

Renin‐like activity of the rat submaxillary gland: characterization and the effect of several drugs and stimuli

Renin‐like activity of the rat submaxillary gland: characterization and the effect of several drugs and stimuli

Method Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry for Angiotensin-II in Human Plasma: Application to Study Interaction Between Atorvastatin & Olmesartan Drug Combination

A visionary scientist selects clinicians for clinical research

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