GABA C receptors in neuroendocrine gut cells: a new GABA-binding site in the gut

Jansen, A.; Hoepfner, Michael; Herzig, Karl‐Heinz; Riecken, E. O.; Scherübl, Hans

doi:10.1007/s004240000412

Cited by 41 publications

(22 citation statements)

References 28 publications

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“…The ρ subunit family is also highly expressed in the retina (Enz et al, 1995). Functional GABAC receptors were also found in several hormone secretory organs, such as the pancreas and the pituitary glands (GamelDidelon et al, 2003;Jansen et al, 2000). Therefore, the necessary subunits needed to assemble a functional GABA A or GABA C receptor are present in fetal pulmonary epithelial cells.…”

Section: Summary and Further Discussionmentioning

confidence: 99%

Ionotropic GABA receptor expression in the lung during development

Jin

Guo

Sun

et al. 2008

Gene Expression Patterns

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Cl − transport is essential for lung development. Because gamma-aminobutyric acid (GABA) receptors allow the flow of negatively-charged Cl − ions across the cell membrane, we hypothesized that the expression of ionotropic GABA receptors are regulated in the lungs during development. We identified 17 GABA receptor subunits in the lungs by real-time PCR. These subunits were categorized into 4 groups: Group 1 had high mRNA expression during fetal stages and low in adults; Group 2 had steady expression to adult stages with a slight up-regulation at birth; Group 3 showed an increasing expression from fetal to adult lungs; and Group 4 displayed irregular mRNA fluctuations. The protein levels of selected subunits were also determined by Western blots and some subunits had protein levels that corresponded to mRNA levels. Further studied subunits were primarily localized in epithelial cells in the developing lung with differential mRNA expression between isolated cells and whole lung tissues. Our results add to the knowledge of GABA receptor expression in the lung during development. Keywordslungs; ionotropic GABA receptor; fetal lung development; chloride homeostasis; lung fluid transport; real time PCR; gene expression; alveolar epithelial cells RESULTS AND DISCUSSION SignificanceCl − channels play an important role in the lung throughout an animal's life. During the fetal stages, the lung is a fluid-secreting organ. The main driving force for fluid secretion is the active secretion of Cl − into the developing lungs. Therefore, Cl − channels are indispensable for fetal lung development and morphogenesis (Folkesson et al., 1998;Olver et al., 2004;Bland and Nielson, 1992). On the other hand, the adult lung is air-filled and maintains a "dry" state. The apical surface is covered by a thin layer of alveolar surface fluid. This layer of fluid is required for the proper air exchange and airway defenses. Cl − channels are also essential for maintaining the composition and volume of the alveolar surface fluid (Brochiero et al., 2004 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Several Cl − channels have previously been studied in the lung. The cystic fibrosis transmembrane conductance regulator (CFTR) (Harris et al., 1991), the voltage-gated Cl − channels, ClC2 (Thiemann et al., 1992), ClC3 (Lamb et al., 2001), and ClC5 (Edmonds et al., 2002, and Na + -K + -Cl − cotransporter (NKCC) (Rochelle et al., 2000) have been detected in fetal lungs, distal airway epithelial cells and alveolar epithelial cells. Some of the channels have been shown to be involved in fluid homeostasis i...

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Section: Summary and Further Discussionmentioning

confidence: 99%

Ionotropic GABA receptor expression in the lung during development

Jin

Guo

Sun

et al. 2008

Gene Expression Patterns

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“…In this study, we show that TRPA1 channel is expressed in the human and mouse duodenum. In order to investigate the possible function we used mouse intestinal neuroendocrine cell line STC-1 as a well-established model for intestinal hormone release (CCK, GLP-1, GIP) [12][13][14][15] and show that activation of TRPA1 channels with mustard oil derived AITC elevates the intracellular Ca 2+ levels and stimulates cholecystokinin release.…”

Section: Introductionmentioning

confidence: 99%

TRPA1 channel activation induces cholecystokinin release via extracellular calcium

et al. 2007

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TRPA1 channels are non-selective cation channels activated by plant derived pungent products including allyl isothiocyanate (AITC) from mustard. Therefore, possible intestinal secretory functions of these channels were investigated. We detected TRPA1 mRNA in mouse and human duodenal mucosa and in intestinal mouse neuroendocrine STC-1 cells. Stimulation of STC-1 cells with AITC increased intracellular calcium ([Ca 2+ ] i ) and significantly stimulated cholecystokinin secretion by 6.7-fold. AITC induced cholecystokinin release was completely blocked by TRPA1 antagonist ruthenium red and depletion of extracellular calcium and reduced by 36% by nimodipine and nifedipine. This suggests that spices in our daily food might stimulate digestive functions.

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“…Furthermore, ρ subunits were detected in secretory cells of the pituitary, in neurons of the gastrointestinal tract and in a neuroendocrine tumour cell line of the gut [37][38][39][40]. These findings suggest that in addition to regulating neurotransmission, GABA C receptors are associated with secretory pathways.…”

Section: Discussionmentioning

confidence: 81%

Tax1-binding protein 1 is expressed in the retina and interacts with the GABAC receptor ρ1 subunit

Ulrich

Seeber

Becker

et al. 2006

Biochemical Journal

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Macromolecular signalling complexes that link neurotransmitter receptors to functionally and structurally associated proteins play an important role in the regulation of neurotransmission. Thus the identification of proteins binding to neurotransmitter receptors describes molecular mechanisms of synaptic signal transduction. To identify interacting proteins of GABA C (where GABA is γ -aminobutyric acid) receptors in the retina, we used antibodies specific for GABA C receptor ρ1-3 subunits. Analysis of immunoprecipitated proteins by MALDI-TOF MS (matrixassisted laser-desorption ionization-time-of-flight MS) identified the liver regeneration-related protein 2 that is identical with amino acids 253-813 of the Tax1BP1 (Tax1-binding protein 1). A Cterminal region of Tax1BP1 bound to an intracellular domain of the ρ1 subunit, but not to other subunits of GABA C , GABA A or glycine receptors. Confocal laser-scanning microscopy demonstrated co-localization of Tax1BP1 and ρ1 in clusters at the cell membrane of transfected cells. Furthermore, Tax1BP1 and GABA C receptors were co-expressed in both synaptic layers of the retina, indicating that Tax1BP1 is a component of GABA C receptor-containing signal complexes.

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GABA C receptors in neuroendocrine gut cells: a new GABA-binding site in the gut

Cited by 41 publications

References 28 publications

Ionotropic GABA receptor expression in the lung during development

Ionotropic GABA receptor expression in the lung during development

TRPA1 channel activation induces cholecystokinin release via extracellular calcium

Tax1-binding protein 1 is expressed in the retina and interacts with the GABAC receptor ρ1 subunit

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