Serotonin Degradation by Ceruloplasmin and Its Inhibition by Isoniazid and Iproniazid*

Zarafonetis, Chris J. D.; Kalas, John P.

doi:10.1097/00000441-196002000-00014

Cited by 28 publications

(6 citation statements)

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“…Meyer and associates [16] have sug gested a role for ceruloplasmin during the rapid proliferation of certain tissue types. Porter [20] has implicated ceruloplasmin in serotonin metabolism and Zarafonetis [26] has studied the de gradation of serotonin by ceruloplasmin.…”

Section: Discussionmentioning

confidence: 99%

Concentration and Purification of Ceruloplasmin from Human Blood Plasma Fractions

Björling¹

1963

Vox Sanguinis

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Section: Discussionmentioning

confidence: 99%

Concentration and Purification of Ceruloplasmin from Human Blood Plasma Fractions

Björling¹

1963

Vox Sanguinis

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“…demonstrated in this laboratory that ill i\itro degradation of serotonin by ceruloplasmin is strongly inhibited by both isoniazid and iproniazid ( 1 ) . This finding may be of importance in connection with the psychopharniacologic and other clinical effects of these compounds.…”

mentioning

confidence: 88%

“…BG, Cizn be estimated in leukocytes and plasma using a modification of the manometric method of Umbreit et d. ( 1 ) . Previously, this has been done in the blood ol f normal (2,3,4) and pregnant subjects(3,4) and in the cord blood of new born babies (3,4).…”

Section: Max Wachstein Jordan D Kellner and Jose M Ortizmentioning

confidence: 99%

Effect of Certain Compounds on in vitro Degradation of Serotonin by Ceruloplasmin.

Zarafonetis

Kalas

1960

Experimental Biology and Medicine

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It was recent&. demonstrated in this laboratory that ill i\itro degradation of serotonin by ceruloplasmin is strongly inhibited by both isoniazid and iproniazid ( 1 ) . This finding may be of importance in connection with the psychopharniacologic and other clinical effects of these compounds. lloreover, it may have significance with regard to a concept which postulates that fibrosis may result from an imbalance between serotonin and serotonin degradation mechanisms a t the tissue level( 1.2.3). Tn 17iew of these and other considerations. it became of interest to determine the in vifro effect of a wide range of other compounds on this pathway of serotonin oxidation.Accordingly, tests were performed with selected reducing, sulfhydryl containing, and metal binding compounds; with hydrazine derivatives and amine oxidase inhibitors ; and with a number of antihypertension and psychopharmacologic agents. The findings form the basis of this report.Muterids utid mefhods. Initial titration tests with purified preparations of ceruloplasmin confirmed the activity of this enzyme over a wide pH range. Although optimal activity was at pH 6.0, it was elected to perform these i~ zdro tests at a more closely physiological pH, that is, 7.4. Accordingly. serial 2-fold dilutions of ceruloplasmin were made in physiological saline solution. The enzyme concentration which was found to metabolize between 65% and 80% of the substrate (300 pg serotonin-creatinine sulfate) was used in the final test system. This degree of enzyme activity was found to be present in a 1:8 dilution of the human ceruloplasmin employed. Dilutions of 3 different preparations of ceruloplasmin were used. These were designated DWZ 37. DWZ 42, and DWZ 44. and had been prepared by the *Aided by a grant from Pennsylvania Trudeau SOC. Kabi Co.. Stockholm, Swedent I'I'OCCdZII'C. To a 20 ml beaker were added 1 .O nil of ceruloplasmin solution; 1.0 ml of 0.5 11 phosphate buffer, pH 7.4; and 0.5 ml of the solution containing the substance to] be tested for inhibition of the reaction. The beakers were pre-incubated for 15 minutes on a Dubnoff metabolic shaker. Solutions of the test substances were freshly prepared and placed in the test system within 10 minutes of preparation. Final concentration in the incubation mixture was 4.9 s hl for serotonin. Incubation was continued for 1 hour, and determination for residual serotonin was made by the colorimetric method of Udenfriend, ct nZ.(4). Controls included tests with boiled ceruloplasmin, and, for color interference, recovery of serotonin after incubation with the respective test substance in absence of enzyme.The following substances were tested for reaction inhibition at a final colncentration of I s 10 M: sodium metabisulfite, ascorbic acid. glutathione, British anti-lewisite ( HA4L), cysteine, methionine, D, L penicillamine, sodium cyanide, and ethylene diamine tetracetic acid (EDTA) , Among the hydrazine derivatives and amolng oxidase inhibitors tested a t the same concentration were: amphetamine, procaine amide, iproniaz...

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“…Bei der Alterung der Thrombocyten in der Blut konserve scheinen neben dem ATP vor allem die Fermente der Glykolyse an Aktivität rasch abzunehmen; gleichzeitig vermindert sich die Fähigkeit zur Retraktion (1,8,16). Wenig beeinflußt wer den dagegen die thrombocytären Gerinnungsfaktoren 3 und 4 so wie die thrombelastographisch gemessene Scherelastizität des plätt chenhaltigen Gerinnsels (8,10 (26) konnten kürzlich nachweisen, daß im frischen Plasma das 5-HT durch Coeruloplasmin oxydativ abgebaut wird. Es bleibt noch zu prüfen, ob die Aktivität dieses Fermentes im Konservenplasma parallel zur sinkenden Serotonin-Inaktivierung zurückgeht.…”

Section: Nach Früheren Untersuchungen Ist Das Bindungsvermögen Derunclassified

Untersuchungen über die Aminbindung bei der Aliening der Blutplättchen

Schmid¹,

Meythaler²,

Witte³

et al. 1961

Acta Haematol

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Serotonin Degradation by Ceruloplasmin and Its Inhibition by Isoniazid and Iproniazid*

Cited by 28 publications

References 0 publications

Concentration and Purification of Ceruloplasmin from Human Blood Plasma Fractions

Concentration and Purification of Ceruloplasmin from Human Blood Plasma Fractions

Effect of Certain Compounds on in vitro Degradation of Serotonin by Ceruloplasmin.

Untersuchungen über die Aminbindung bei der Aliening der Blutplättchen

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