Regulation of gastric mucosal diamine oxidase activity by gastrin

Hougaard, David M.; Larsson, Lars‐Inge

doi:10.1016/0014-5793(92)80752-3

Cited by 10 publications

(5 citation statements)

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“…Feeding of rats with specific gastric nutrients increases antral gastrin mRNA levels and decreases somatostatin mRNA levels, whereas fasting has the opposite effect (Wu et al 1991). Our present results show that the numbers of DAO-immunoreactive cells are increased during fasting, which agrees with studies showing that fasting increases DAO-catalyzed formation of GABA from putrescine in the rat stomach (Hougaard et al 1992). It is therefore tempting to speculate that gastrin cells may relieve the tonic restraint on gastrin secretion by paracrine release of GABA, which would serve to inhibit the secretion of somatostatin.…”

Section: Discussionsupporting

confidence: 90%

“…It is formed by decarboxylation of ornithine and during the degradation of polyamines. In many tissues, including liver, kidney, adrenal gland, pancreatic islets, intestine, and stomach, putrescine also serves as substrate for diamine oxidase (DAO) (Seiler 1980;Oon et al 1989;Hougaard et al 1986Hougaard et al , 1992. The oxidation of putrescine leads to formation of ␥ -aminobutyric aldehyde, which is further converted to ␥ -aminobutyric acid (GABA) by aldehyde dehydrogenase (Seiler 1980).…”

mentioning

confidence: 99%

“…However, it has not been possible to demonstrate GAD in antropyloric somatostatin and gastrin cells (Gilon et al 1991). Because of this, and because feeding and exogenous gastrin inhibit DAO-catalyzed formation of GABA from putrescine in the rat stomach (Hougaard et al 1992), we have investigated if DAO is present in antropyloric somatostatin and gastrin cells and whether the immunohistochemical staining is affected by the prandial state.…”

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confidence: 99%

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Immunocytochemical Evidence Suggesting that Diamine Oxidase Catalyzes Biosynthesis of γ-Aminobutyric Acid in Antropyloric Gastrin Cells

Hardt

Larsson²,

Hougaard

2000

J Histochem Cytochem.

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S U M M A R Y ␥ -Aminobutyric acid (GABA) is a neurotransmitter that also occurs in a few non-neuronal cell types, where it may serve as a paracrine modulator. GABA is biosynthesized from glutamate by glutamate decarboxylase (GAD) and from putrescine via diamine oxidase (DAO). GAD is demonstrable in several GABA-positive cell types but is undetectable in the GABA-containing gastrin cells and somatostatin cells of the antropyloric mucosa of the stomach. Using two antisera raised against synthetic peptides corresponding to two different regions of rat DAO, we now demonstrate strong reactivity for DAO in gastrinpositive cells of the rat antropyloric mucosa, whereas somatostatin-positive cells as well as other structures of the antrum are unreactive. Western blotting analysis of antrum and colon demonstrate that both antisera react with a single band of 85 kD, consistent with the predicted molecular weight of DAO. Expression of DAO mRNA in the antrum is demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR). Our results strongly indicate that gastrin cells produce GABA via DAO-catalyzed oxidation of putrescine, and experimental data moreover suggest that the biosynthesis of GABA is regulated by the prandial state. Because GABA modulates release of somatostatin, these results point to a new mechanism of paracrine interaction between gastrin cells and somatostatin cells.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

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confidence: 99%

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Immunocytochemical Evidence Suggesting that Diamine Oxidase Catalyzes Biosynthesis of γ-Aminobutyric Acid in Antropyloric Gastrin Cells

Hardt

Larsson²,

Hougaard

2000

J Histochem Cytochem.

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“…Moreover, GABA obtained from this pathway in gastrin-producing enteroendocrine cells is a postulated paracrine modulator within the gastric mucosa (44,45). These findings, together with the observations that (i) ABP1 is cell membrane-associated (46,47) and (ii) its mRNA is called ''Present'' almost exclusively in poorvs.…”

Section: Generation Of Metabolic Signatures Indicative Of Poor-prognosismentioning

confidence: 60%

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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“…3). GABA derived from this pathway is proposed to be a paracrine signaling molecule exported by enteroendocrine cells in the gastric mucosa [114,115]. Increased ABP1 activity has been demonstrated in NE carcinomas including small cell lung carcinomas and medullary thyroid carcinoma [40,116].…”

Section: Gaba Biosynthesismentioning

confidence: 99%

Current concepts in neuroendocrine cancer metabolism

Ippolito

2006

Pituitary

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Neuroendocrine (NE) cancers occur in multiple anatomic locations and range in prognosis from indolent to aggressive. In addition, adenocarcinomas can express gene products associated with NE cells, referred to as NE differentiation (NED), which correlates with poor prognosis and aggressive disease. Several metabolites and peptides produced by NE cells have been discovered that engage in cellular signaling and have autocrine and paracrine effects on cancer cell proliferation. This review focuses on the current knowledge of small molecule metabolism in NE cancers involving the synthesis of biogenic amine, polyamine, and amino acid neurotransmitters. Systems biology-directed approaches to NE cancer metabolism using gene expression profiling, liquid chromatography/mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR) are also discussed. Furthermore, knowledge of metabolic and signaling pathways in NE cancers has led to the successful implementation of therapeutic regimens in cell culture and animal models of NE carcinogenesis.

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Regulation of gastric mucosal diamine oxidase activity by gastrin

Cited by 10 publications

References 20 publications

Immunocytochemical Evidence Suggesting that Diamine Oxidase Catalyzes Biosynthesis of γ-Aminobutyric Acid in Antropyloric Gastrin Cells

Immunocytochemical Evidence Suggesting that Diamine Oxidase Catalyzes Biosynthesis of γ-Aminobutyric Acid in Antropyloric Gastrin Cells

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

Current concepts in neuroendocrine cancer metabolism

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