Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

Decreased Platelet Monoamine Oxidase Activity in Chronic Schizophrenia, Shown With Novel Substrates

Decreased Platelet Monoamine Oxidase Activity in Chronic Schizophrenia, Shown With Novel Substrates Abstract • Platelet monoamine oxidase (MAO) was kinetically evaluated in chronic schizophrenics and matched controls, using substrates of major physiologic importance and substrates of particular interest in the study of schizophrenia, such as serotonin (5-HT),N,N-dimethyltryptamine(DMT), 5-methoxytryptamine (5-MT), and dopamine (DA). Substrates were measured at six concentrations; values for maximal velocity (Vmax) and Michaelis constant (Km) were obtained by using Lineweaver-Burk plots. The Vmax was decreased for all substrates in chronic schizophrenia and the Km was decreased for DA, 5-HT, and DMT, but remained unchanged for 5-MT. The value of Km/Vmax was similar for schizophrenics and normal persons when DA, 5-HT, and DMT were used as substrates, which may indicate that "uncompetitive" inhibition is responsible for the observed decrease in activity among chronic schizophrenics. The finding of a decreased Vmax but unchanged Km with 5-MT would be consistent with noncompetitive inhibition. References 1. Berrettini WH, Vogel WH, Clouse R: Platelet monoamine oxidase in chronic schizophrenia . Am J Psychiatry 134:805-806, 1977. 2. Domino EF, Khanna SS: Decreased blood platelet MAO activity in unmedicated chronic schizophrenic patients . Am J Psychiatry 133:323-326, 1977. 3. Schildkraut JJ, Herzog JM, Orsulak PJ, et al: Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients . Am J Psychiatry 133:438-440, 1976. 4. Murphy DL, Donnelly CH, Miller L, et al: Platelet monoamine oxidase in chronic schizophrenia . Arch Gen Psychiatry 33:1377-1381, 1976.Crossref 5. Murphy DL, Belmaker R, Wyatt RJ: Monoamine oxidase acitivty in schizophrenia and other behavioral disorders . J Psychiatr Res 11:221-247, 1974.Crossref 6. Wyatt RJ, Murphy DL, Belmaker R, et al: Reduced monoamine oxidase in platelets: A possible genetic marker for vulnerability to schizophrenia . Science 179:916-918, 1973.Crossref 7. Meltzer HY, Stahl SM: Platelet monoamine oxidase activity and substrate preferences in schizophrenic patients . Res Commun Chem Pathol Pharmacol 7:419-431, 1974. 8. Murphy DL, Wyatt RJ: Reduced monoamine oxidase acitivity in blood platelets from schizophrenic patients . Nature 238:225-226, 1972.Crossref 9. Nies A, Robinson DS, Harris LS, et al: Comparison of monoamine oxidase substrate activities in twins, schizophrenics, depressives and controls , in Usdin E (ed): Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes . New York, Raven Press, 1974, pp 59-70. 10. Owen F, Bourne R, Crow TJ, et al: Platelet MAO in schizophrenia . Arch Gen Psychiatry 33:1370-1373, 1976.Crossref 11. Brockington I, Crow TJ, Johnstone EC, et al: An investigation of platelet monoamine oxidase activity in schizophrenia and schizo-affective psychosis , in Wolstenholme GEW, Knight J (eds): Monoamine Oxidase and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 353-363. 12. Shaskan EG, Becker RE: Platelet monoamine oxidase in schizophrenics . Nature 253:659-660, 1975.Crossref 13. Friedman E, Shopsin B, Sathananthan G, et al: Blood platelet monoamine oxidase activity in psychiatric patients . Am J Psychiatry 131:1392-1394, 1974. 14. White HL, McCleod MN, Davidson JRT: Platelet monoamine oxidase activity in schizophrenia . Am J Psychiatry 133:1191-1193, 1976. 15. Wyatt RJ: The transmethylation hypothesis: A quarter of a century later . Psychiatr Ann 6:36-46, 1976. 16. Matthysse S: Dopamine and the pharmacology of schizophrenia: The state of the evidence . J Psychiatr Res 11:107-120, 1974.Crossref 17. Mandel LR, Prasad R, Lopez-Ramos B, et al: The biosynthesis of DMT in vitro . Res Commun Chem Pathol Pharmacol 16:47-58, 1977. 18. Narasimhachari N, Baumann P, Pak SH, et al: Gas chromatographic mass spectrometric identification of urinary bufotenine and DMT in drugfree chronic schizophrenics . Biol Psychiatry 8:293-305, 1974. 19. Wyatt RJ, Mandel LR, Ahn HS, et al: Gas chromatographic-mass spectrometric isotope dilution determination of N-N-dimethyltryptamine concentrations in normal and psychiatric patients . Psychopharmacologia 31:265-270, 1973.Crossref 20. Prozialeck W: The fluorometric determination of 5-MT in mammalian tissue . J Neurochem , to be published. 21. Prozialeck W, Vogel WH: MAO inhibition and the effects of centrally administered LSD, Brom LSD, serotonin and 5-MT on the conditioned avoidance response in rats . Soc Neurosci Abstr 3:447, 1977. 22. Koslow SH, Post R, Goodwin F, et al: Mass fragmentographci identification and quantification of 5-MT in human CSF . Soc Neurosci Abstr 1:361, 1975. 23. Report of the International Pilot Study of Schizophrenia. Geneva, 1973. 24. Callender S, Grahame-Smith DG, Woods HF, et al: Reduction of platelet monoamine oxidase in iron deficiency anemia . Br J Pharmacol 52:447-448, 1974. 25. Lowry OH, Rosebrough MJ, Farr AL, et al: Protein measurement with the folin phenol reagent . J Biol Chem 193:265-275, 1951. 26. Wurtman RJ, Axelrod J: A sensitive and specific assay for the estimation of MAO . Biochem Pharmacol 12:1439-1441, 1963.Crossref 27. Tipton KF, Youdim MBH: Assay of MAO , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 393-403. 28. Kveder S, McIsaac WM: The metabolism of melatonin and 5-methoxytryptamine . J Biol Chem 236:3214-3220, 1961. 29. Maickel RP, Miller FP: Fluorescent products formed by reaction of indole derivatives and O-phthalaldehydes . Anal Chem 38:1937-1938, 1966.Crossref 30. Cohen I, Vogel WH: An assay procedure for mescaline and its determination in rat brain, liver and plasma . Experientia 26:1231-1232, 1970.Crossref 31. Robinson DS, Lovenberg W, Keiser H, et al: Effects of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo . Biochem Pharmacol 17:109-119, 1968.Crossref 32. Edwards DJ, Chang SS: Multiple forms of MAO in rabbit platelets . Life Sci 17:1127-1134, 1975.Crossref 33. Glover V, Sandler M: Dopamine is a MAO B substrate in man . Nature 265:80-81, 1977.Crossref 34. Collins GGS, Sandler M: Human blood platelet monoamine oxidase . Biochem Pharmacol 20:289-296, 1971.Crossref 35. Dixon M, Webb EC: The Enzymes . New York, Academic Press Inc, 1964, p 324. 36. Tipton KF, Housley MD, Mantle TJ: The nature and location of the multiple forms of MAO , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 5-15. 37. Murphy DL: Clinical, genetic, hormonal and drug influences on the activity of human platelet MAO , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 341-351. 38. Yang H-YT, Neff NH: The monoamine oxidases of brain, selective inhibition with drugs and the consequences for the metabolism of biogenic amines . J Pharmacol Exp Ther 189:733-740, 1974. 39. Prozialeck W, Vogel WH: Metabolism of 5-methoxytryptamine, serotonin and phenylethylamine by rat MAO in vivo and in vitro : Life Sci 22:561-570, 1978.Crossref 40. Youdim MBH, Collins GGS, Sandler M, et al: Human brain monoamine oxidase: Multiple forms and selective inhibitors . Nature 236:225-228, 1972.Crossref 41. Green AK, Youdim MBH: Use of a behavioral model to study the action of MAO inhibiton in vivo , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 231-240. 42. Murphy DL, Donnelly CH: MAO in man: Enzyme characteristics in platelets, plasma and other human tissues , in Usdin E (ed): Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes . New York, Raven Press, 1974, pp 71-85. 43. Nies A, Robinson DS, Lamborn KR, et al: Genetic control of platelet and plasma MAO activity . Arch Gen Psychiatry 28:834-838, 1973.Crossref 44. Schwartz MA, Wyatt RJ, Hsiu-Ying TY, et al: Multiple forms of brain monoamine oxidase in schizophrenic and normal individuals . Arch Gen Psychiatry 31:557-560, 1974.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Decreased Platelet Monoamine Oxidase Activity in Chronic Schizophrenia, Shown With Novel Substrates

Loading next page...
 
/lp/american-medical-association/decreased-platelet-monoamine-oxidase-activity-in-chronic-schizophrenia-Sp1kVimpCk
Publisher
American Medical Association
Copyright
Copyright © 1978 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1978.01770290082007
Publisher site
See Article on Publisher Site

Abstract

Abstract • Platelet monoamine oxidase (MAO) was kinetically evaluated in chronic schizophrenics and matched controls, using substrates of major physiologic importance and substrates of particular interest in the study of schizophrenia, such as serotonin (5-HT),N,N-dimethyltryptamine(DMT), 5-methoxytryptamine (5-MT), and dopamine (DA). Substrates were measured at six concentrations; values for maximal velocity (Vmax) and Michaelis constant (Km) were obtained by using Lineweaver-Burk plots. The Vmax was decreased for all substrates in chronic schizophrenia and the Km was decreased for DA, 5-HT, and DMT, but remained unchanged for 5-MT. The value of Km/Vmax was similar for schizophrenics and normal persons when DA, 5-HT, and DMT were used as substrates, which may indicate that "uncompetitive" inhibition is responsible for the observed decrease in activity among chronic schizophrenics. The finding of a decreased Vmax but unchanged Km with 5-MT would be consistent with noncompetitive inhibition. References 1. Berrettini WH, Vogel WH, Clouse R: Platelet monoamine oxidase in chronic schizophrenia . Am J Psychiatry 134:805-806, 1977. 2. Domino EF, Khanna SS: Decreased blood platelet MAO activity in unmedicated chronic schizophrenic patients . Am J Psychiatry 133:323-326, 1977. 3. Schildkraut JJ, Herzog JM, Orsulak PJ, et al: Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients . Am J Psychiatry 133:438-440, 1976. 4. Murphy DL, Donnelly CH, Miller L, et al: Platelet monoamine oxidase in chronic schizophrenia . Arch Gen Psychiatry 33:1377-1381, 1976.Crossref 5. Murphy DL, Belmaker R, Wyatt RJ: Monoamine oxidase acitivty in schizophrenia and other behavioral disorders . J Psychiatr Res 11:221-247, 1974.Crossref 6. Wyatt RJ, Murphy DL, Belmaker R, et al: Reduced monoamine oxidase in platelets: A possible genetic marker for vulnerability to schizophrenia . Science 179:916-918, 1973.Crossref 7. Meltzer HY, Stahl SM: Platelet monoamine oxidase activity and substrate preferences in schizophrenic patients . Res Commun Chem Pathol Pharmacol 7:419-431, 1974. 8. Murphy DL, Wyatt RJ: Reduced monoamine oxidase acitivity in blood platelets from schizophrenic patients . Nature 238:225-226, 1972.Crossref 9. Nies A, Robinson DS, Harris LS, et al: Comparison of monoamine oxidase substrate activities in twins, schizophrenics, depressives and controls , in Usdin E (ed): Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes . New York, Raven Press, 1974, pp 59-70. 10. Owen F, Bourne R, Crow TJ, et al: Platelet MAO in schizophrenia . Arch Gen Psychiatry 33:1370-1373, 1976.Crossref 11. Brockington I, Crow TJ, Johnstone EC, et al: An investigation of platelet monoamine oxidase activity in schizophrenia and schizo-affective psychosis , in Wolstenholme GEW, Knight J (eds): Monoamine Oxidase and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 353-363. 12. Shaskan EG, Becker RE: Platelet monoamine oxidase in schizophrenics . Nature 253:659-660, 1975.Crossref 13. Friedman E, Shopsin B, Sathananthan G, et al: Blood platelet monoamine oxidase activity in psychiatric patients . Am J Psychiatry 131:1392-1394, 1974. 14. White HL, McCleod MN, Davidson JRT: Platelet monoamine oxidase activity in schizophrenia . Am J Psychiatry 133:1191-1193, 1976. 15. Wyatt RJ: The transmethylation hypothesis: A quarter of a century later . Psychiatr Ann 6:36-46, 1976. 16. Matthysse S: Dopamine and the pharmacology of schizophrenia: The state of the evidence . J Psychiatr Res 11:107-120, 1974.Crossref 17. Mandel LR, Prasad R, Lopez-Ramos B, et al: The biosynthesis of DMT in vitro . Res Commun Chem Pathol Pharmacol 16:47-58, 1977. 18. Narasimhachari N, Baumann P, Pak SH, et al: Gas chromatographic mass spectrometric identification of urinary bufotenine and DMT in drugfree chronic schizophrenics . Biol Psychiatry 8:293-305, 1974. 19. Wyatt RJ, Mandel LR, Ahn HS, et al: Gas chromatographic-mass spectrometric isotope dilution determination of N-N-dimethyltryptamine concentrations in normal and psychiatric patients . Psychopharmacologia 31:265-270, 1973.Crossref 20. Prozialeck W: The fluorometric determination of 5-MT in mammalian tissue . J Neurochem , to be published. 21. Prozialeck W, Vogel WH: MAO inhibition and the effects of centrally administered LSD, Brom LSD, serotonin and 5-MT on the conditioned avoidance response in rats . Soc Neurosci Abstr 3:447, 1977. 22. Koslow SH, Post R, Goodwin F, et al: Mass fragmentographci identification and quantification of 5-MT in human CSF . Soc Neurosci Abstr 1:361, 1975. 23. Report of the International Pilot Study of Schizophrenia. Geneva, 1973. 24. Callender S, Grahame-Smith DG, Woods HF, et al: Reduction of platelet monoamine oxidase in iron deficiency anemia . Br J Pharmacol 52:447-448, 1974. 25. Lowry OH, Rosebrough MJ, Farr AL, et al: Protein measurement with the folin phenol reagent . J Biol Chem 193:265-275, 1951. 26. Wurtman RJ, Axelrod J: A sensitive and specific assay for the estimation of MAO . Biochem Pharmacol 12:1439-1441, 1963.Crossref 27. Tipton KF, Youdim MBH: Assay of MAO , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 393-403. 28. Kveder S, McIsaac WM: The metabolism of melatonin and 5-methoxytryptamine . J Biol Chem 236:3214-3220, 1961. 29. Maickel RP, Miller FP: Fluorescent products formed by reaction of indole derivatives and O-phthalaldehydes . Anal Chem 38:1937-1938, 1966.Crossref 30. Cohen I, Vogel WH: An assay procedure for mescaline and its determination in rat brain, liver and plasma . Experientia 26:1231-1232, 1970.Crossref 31. Robinson DS, Lovenberg W, Keiser H, et al: Effects of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo . Biochem Pharmacol 17:109-119, 1968.Crossref 32. Edwards DJ, Chang SS: Multiple forms of MAO in rabbit platelets . Life Sci 17:1127-1134, 1975.Crossref 33. Glover V, Sandler M: Dopamine is a MAO B substrate in man . Nature 265:80-81, 1977.Crossref 34. Collins GGS, Sandler M: Human blood platelet monoamine oxidase . Biochem Pharmacol 20:289-296, 1971.Crossref 35. Dixon M, Webb EC: The Enzymes . New York, Academic Press Inc, 1964, p 324. 36. Tipton KF, Housley MD, Mantle TJ: The nature and location of the multiple forms of MAO , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 5-15. 37. Murphy DL: Clinical, genetic, hormonal and drug influences on the activity of human platelet MAO , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 341-351. 38. Yang H-YT, Neff NH: The monoamine oxidases of brain, selective inhibition with drugs and the consequences for the metabolism of biogenic amines . J Pharmacol Exp Ther 189:733-740, 1974. 39. Prozialeck W, Vogel WH: Metabolism of 5-methoxytryptamine, serotonin and phenylethylamine by rat MAO in vivo and in vitro : Life Sci 22:561-570, 1978.Crossref 40. Youdim MBH, Collins GGS, Sandler M, et al: Human brain monoamine oxidase: Multiple forms and selective inhibitors . Nature 236:225-228, 1972.Crossref 41. Green AK, Youdim MBH: Use of a behavioral model to study the action of MAO inhibiton in vivo , in MAO and its Inhibition . New York, Elsevier Publishing Co, 1976, pp 231-240. 42. Murphy DL, Donnelly CH: MAO in man: Enzyme characteristics in platelets, plasma and other human tissues , in Usdin E (ed): Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes . New York, Raven Press, 1974, pp 71-85. 43. Nies A, Robinson DS, Lamborn KR, et al: Genetic control of platelet and plasma MAO activity . Arch Gen Psychiatry 28:834-838, 1973.Crossref 44. Schwartz MA, Wyatt RJ, Hsiu-Ying TY, et al: Multiple forms of brain monoamine oxidase in schizophrenic and normal individuals . Arch Gen Psychiatry 31:557-560, 1974.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: May 1, 1978

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$499/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month