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- W1997554865 abstract "Background: Somatostatin (SS) inhibits both basal and gastrin stimulated histamine release from ECL cells in gastric mucosa. This is mediated through the SSTR2 receptor in human and rat antral mucosal strips. Histidine decarboxylase (HDC) is the enzyme responsible for histamine production in ECL cells and has previously been shown to be transcriptionally regulated through a gastrin response element. We postulated that SS may regulate the HDC promoter. The mechanisms through which SS may alter HDC transcription have not been elucidated. Methods: AGS-B cells were transfected with a plasmid containing 1.8 kb of the 5' promoter region of hHDC upsteam of the firefly luciferase reporter (1.8 kb hHDC-luc). Plasmids containing the cDNA of either human or rat SSTR2 were co-transfected. The cells were stimulated with 10 -7 M of gastrin, phothol ester (PMA) and dose responses with SS or octreotide were done. In addition overexpression of phosphatase SHP-1 and the G protein subunits Gictl and Gict3 were done using plasmids with the respective cDNA. Results.: Overexpression of both human and rat SSTR2 resulted in a dose dependent inhibition of hHDC transcription as measured by a luminometer. Maximal inhibition caused a 80% reduction in HDC transcription. This was seen in basal conditions, as well as with gastrin and PMA stimulated cells. Co-transfection with SHP-1 or its mutant did not block this effect. This inhibitory effect was not overcome with the phosphatase inhibitors sodium orthovanadate or okadaic acid. Addition of receptor agonists SS or octreotide resulted in a dose dependent 2-3 fold stimulation of HDC-Iuc activity. SS mediated stimulation in stably transfected cells was not altered by overexpression of GiQtl and Gia 3, suggesting that this paradoxical effect was not due to a lack of these subunits in AGS-B cells. Conclusions: SSTR2 has an inhibitory effect on HDC transcription in basal and stimulated AGS-B cells. This inhibition by the receptor is not mediated through a phosphatase pathway. Addition of agonists SS and octreotide produces a dose dependent stimulation in transcription of HDC. This is not due to a lack of the appropiate G i subunits in AGS-B cells. SS stimulates HDC transcription independently of G i pathway in AGS-B cells." @default.
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- W1997554865 date "1998-04-01" @default.
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- W1997554865 title "Somatostatin type 2 receptor (SSTR2) inhibition of histidine decarboxylase (HDC) transcription is not mediated through a phosphatase pathway in the human gastric cancer cell line AGS-B" @default.
- W1997554865 doi "https://doi.org/10.1016/s0016-5085(98)84672-6" @default.
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