Biogenic Amine-Aldehyde Condensation Products: Tetrahydroisoquinolines and Tryptolines (szlig-Carbolines)

Deitrich, Richard A.; Erwin, V. Gene

doi:10.1146/annurev.pa.20.040180.000415

Cited by 140 publications

(36 citation statements)

References 66 publications

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“…Our findings suggest that noninvasive imaging modalities such as positron emission tomography (48) and magnetic resonance spectroscopy (49) may be useful for phenotyping patient populations with NE tumors based on the activity of key enzymes in these metabolic pathways (e.g., DDC) and their metabolic products (e.g., GABA). Moreover, GABA, imidazole-4-acetate, and indole-3-acetate may only be a subset of products of these pathways; ABP1-derived aldehydes may react with amine-containing compounds in tumor cells to form precursors for alkaloids similar to those found in plants and other organisms (50).…”

Section: Generation Of Metabolic Signatures Indicative Of Poor-prognosismentioning

confidence: 99%

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

Ippolito

Jain

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

104

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Human neuroendocrine (NE) cancers range from relatively indolent to highly aggressive. In this study, we combine functional genomics with metabolomics to identify features of NE cancers associated with a poor outcome. Analysis of GeneChip datasets of primary prostate tumors, as well as lymph node and liver metastases from transgenic mice with a NE cell cancer, plus derived NE cell lines yielded a signature of 446 genes whose expression is enriched in neoplastic mouse prostatic NE cells. This signature was used for in silico metabolic reconstructions of NE cell metabolism, directed liquid chromatography͞tandem MS analysis of metabolites in prostatic NE tumors and cell lines, and analysis of GeneChip datasets of human NE tumors with good or poor prognoses. The results indicate that a distinguishing feature of poor-prognosis NE tumors is a glutamic acid decarboxylase-independent pathway for production of GABA and a pathway for production of imidazole-4-acetate that involves dopa decarboxylase and a membraneassociated amine oxidase, amiloride-binding protein 1. Electrophysiological studies disclosed that imidazole-4-acetate can bind and activate GABAA receptors expressed by transformed NE cells, thus providing a previously uncharacterized paradigm for NE tumor cell signaling. Transcriptional, metabolic, and electrophysiologic features of transformed mouse NE cells are also evident in neural progenitor cells.GABA signaling ͉ MS ͉ metastatic neuroendocrine cancers ͉ polyamine metabolism ͉ transcriptome-directed metabolomics H uman neuroendocrine (NE) cancers (NECs) can arise in neuroectodermal tissues or in endoderm-derived epithelia (e.g., pheochromocytomas and small cell lung cancers, respectively). Many types of NECs are aggressive and diagnosed only after metastatic spread (1, 2). In addition, the appearance of NE features in cancers arising from cells that do not normally express neural or endocrine fates is often associated with more aggressive disease (3-5). A panel of biomarkers and mediators of tumorigenesis is needed for better diagnosis and stratification of NECs and new, more efficacious therapeutic approaches. In this report, we present one approach for addressing this issue that uses a combination of transgenic mice with a metastatic cancer arising from their prostatic NE cell lineage, NE cell lines established from this cancer, human NE tumors with varying degrees of aggressiveness, functional genomics, and MS-based metabolomics.The prostate contains three epithelial lineages: secretory, basal, and NE (6). The secretory or luminal cell is the most abundant type and requires continuous exposure to androgens for its survival (7-11). Basal cells represent the primary proliferating epithelial population and are not androgen-dependent (12, 13). NE cells are rare (Ͻ1% of the total), have distinctive projections that allow them to contact epithelial neighbors located several cell diameters away, and secrete a variety of neuropeptides and neurotransmitters (14-17). Conventional adenocarcinoma of the prostate (C...

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Section: Generation Of Metabolic Signatures Indicative Of Poor-prognosismentioning

confidence: 99%

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

Ippolito

Jain

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

104

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“…Substituted THBC's may be formed by condensation of an aldehyde with substituted tryptamines such as serotonin (5-hydroxytryptamine, 5-HT). Interest in these compounds and the related tetrahydroisoquinoline alkaloids derived from aldehyde-catecholamine condensation has centred largely on their possible endogenous production following ethanol consumption (Deitrich and Erwin 1980). It is notable that members of both the THBC and tetrahydroisoquinoline class of alkaloids have recently been reported to occur in foodstuffs such as fruit and fermented beverages (Duncan and Smythe 1982;Beck et al 1983).…”

Section: Introductionmentioning

confidence: 99%

“…Evidence has been presented suggesting that alkaloids of the THBC class may occur endogenously and are able to effect a wide range of neurochemical, neuroendocrine and behavioural actions (Buckholtz 1980a;Deitrich and Erwin 1980;Barker et al 1981;Rommelspacher et al 1982). In particular, 6-methoxy-1,2,3,4-tetrahydro-p-carboline (6-MeOTHBC) has been well studied and has been reported to be present endogenously in rat brain and adrenal tissue (Barker et al 1981) and has been shown to cause increased secretion of corticosterone in mice (Meyer and Buckholtz 1976).…”

Section: Introductionmentioning

confidence: 99%

Effects of 6-Methoxy-l,2,3,4-tetrahydro-b-carboline and Yohimbine on Hypothalamic Monoamine Status and Pituitary Hormone Release in the Rat

Smythe¹,

Duncan²,

Bradshaw³

et al. 1983

Aust. Jnl. Of Bio. Sci.

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Shortly after administration of 6-methoxy-1,2,3,4-tetrahydro-ft-carboline (6-MeOTHBC) and yohimbine to normal or hypothyroid rats [the latter exhibiting chronically elevated levels of serotonin (5-HT) neuronal activity in the hypothalamus] there was a highly significant increase in hypothalamic noradrenaline (NA) activity and in ACTH release concomittant with a reduction in hypothalamic 5-HT activity (P< 0'01) and in growth hormone (GH) (P

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“…1), may be formed by cyclization of indoleamines with aldehydes in the brain (Deitrich and Erwin, 1980) during conventional high-temperature cooking and tobacco smoking (Pfau and Skog, 2004;Breyer-Pfaff et al, 1996). Harman and norharman are also found in groundwater, plants, grape juice and wine (Allen and Holmstedt, 1980;Pfau and Skog, 2004).…”

Section: Introductionmentioning

confidence: 99%

The Harman and Norharman Reduced Dopamine Content and Induced Cytotoxicity in PC12 Cells

Yang¹,

Lim²,

Lee³

2008

Biomolecules and Therapeutics

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-The effects of harman and norharman on dopamine content and L-DOPA-induced cytotoxicity were investigated in PC12 cells. Harman and norharman decreased the intracellular dopamine content for 24 h. The IC 50 values of harman and norharman were 20.4 µM and 95.8 µM, respectively. Tyrosine hydroxylase (TH) activity and TH mRNA levels were also decreased by 20 µM harman and 100 µM norharman. Under the same conditions, the intracellular cyclic AMP levels were decreased by harman and norharman. In addition, harman and norharman at concentrations higher than 80 µM and 150 µM caused cytotoxicity at 24 h in PC12 cells. Non-cytotoxic ranges of 10-30 µM harman and 50-150 µM norharman inhibited L-DOPA (20-50 µM)-induced increases of dopamine content at 24 h. Harman at 20-150 µM and norharman at 100-300 µM also enhanced L-DOPA (20-100 µM)-induced cytotoxicity at 24 h. These results suggest that harman and norharman decrease dopamine content by reducing TH activity and aggravate L-DOPA-induced cytotoxicity in PC12 cells.

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Biogenic Amine-Aldehyde Condensation Products: Tetrahydroisoquinolines and Tryptolines (szlig-Carbolines)

Cited by 140 publications

References 66 publications

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

Effects of 6-Methoxy-l,2,3,4-tetrahydro-b-carboline and Yohimbine on Hypothalamic Monoamine Status and Pituitary Hormone Release in the Rat

The Harman and Norharman Reduced Dopamine Content and Induced Cytotoxicity in PC12 Cells

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