This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerhard, M. Articles by Prinz, C. Search for Related Content PubMed PubMed Citation Articles by Gerhard, M. Articles by Prinz, C.

Gastrin Induces Expression and Promoter Activity of the Vesicular Monoamine Transporter Subtype 2

II Medizinische Klinik (M.G., N.N., E.P.-S., R.Z., C.P.) and Department of Obstetrics and Gynecology (E.L.), Technical University, D-81675 Munich, Germany; and Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Universitätsklinikum Charite, Campus Virchow-Klinikum (T.C., M.H.), D-13353 Berlin, Germany

Address all correspondence and requests for reprints to: Dr. Christian Prinz, II Medizinische Klinik, Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany. E-mail: christian. prinz{at}lrz.tum.de

Gastric enterochromaffin-like cells produce histamine in response to the antral hormone gastrin and accumulate the biogenic amine in secretory organelles via vesicular monoamine transporter subtype 2. The putative effects of gastrin on vesicular monoamine transporter subtype 2 expression and promoter activity are poorly understood. In the present study we used highly enriched rat enterochromaffin-like cells (purity, >90%) and rat pheochromocytoma cells stably transfected with a gastrin/cholecystokinin B receptor to investigate the expression and transcriptional regulation of vesicular monoamine transporter subtype 2. Stimulation of vesicular monoamine transporter subtype 2 mRNA and protein expression was observed in isolated enterochromaffin-like cells after 3- to 7-h incubation with gastrin (10^-7 M), forskolin (10^-5 M), or ionomycin (10^-5 M). Deletion analysis of the rat vesicular monoamine transporter subtype 2 promoter defined the minimal promoter sequence necessary for full basal activity as a -121 bp segment upstream of exon 1 containing two Sp1 sites (-97 to -88 bp and -68 to -59 bp) and a cAMP-responsive element (-44 to -35 bp). Gastrin (10^-7 M) stimulated extracellular signal related kinase1/2 phosphorylation, activated Sp1 and cAMP-responsive element-binding protein, and further induced activity of the complete rat vesicular monoamine transporter subtype 2 promoter (-800 bp) in gastrin/cholecystokinin B receptor cells. The -121-bp fragment was able to confer full gastrin responsiveness, and site-directed mutagenesis of the Sp1 and cAMP-responsive element motifs demonstrated their crucial importance for basal and inducible activities. Comparison of promoter activity of histidine decarboxylase, chromogranin A, or vesicular monoamine transporter subtype 2 in transfected cell lines revealed significant differences in basal and gastrin-stimulated activities. Our current study provides the first evidence that gastrin directly stimulates the expression and promoter activity of vesicular monoamine transporter subtype 2. Sp1 and cAMP-responsive element-binding protein recognition motifs located within 121 bp upstream of exon 1 appear to be indispensable for full basal and inducible promoter activities. Diverging effects of gastrin on histidine decarboxylase, chromogranin A, and vesicular monoamine transporter subtype 2 promoter may account for the coordinated synthesis and storage of histamine in this neuroendocrine cell type.

This article has been cited by other articles:

				W. Ai, H. Zheng, X. Yang, Y. Liu, and T. C. Wang Tip60 functions as a potential corepressor of KLF4 in regulation of HDC promoter activity Nucleic Acids Res., September 25, 2007; 35(18): 6137 - 6149. [Abstract] [Full Text] [PDF]

				K. Catlow, H. L. Ashurst, A. Varro, and R. Dimaline Identification of a Gastrin Response Element in the Vesicular Monoamine Transporter Type 2 Promoter and Requirement of 20 S Proteasome Subunits for Transcriptional Activity J. Biol. Chem., June 8, 2007; 282(23): 17069 - 17077. [Abstract] [Full Text] [PDF]

				R. N. Jain and L. C. Samuelson Transcriptional profiling of gastrin-regulated genes in mouse stomach Physiol Genomics, March 14, 2007; 29(1): 1 - 12. [Abstract] [Full Text] [PDF]

				W. Ai, Y. Liu, and T. C. Wang Yin yang 1 (YY1) represses histidine decarboxylase gene expression with SREBP-1a in part through an upstream Sp1 site Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1096 - G1104. [Abstract] [Full Text] [PDF]

				R. N. Jain, C. S. Brunkan, C. S. Chew, and L. C. Samuelson Gene expression profiling of gastrin target genes in parietal cells Physiol Genomics, January 12, 2006; 24(2): 124 - 132. [Abstract] [Full Text] [PDF]

				W. Ai, Y. Liu, M. Langlois, and T. C. Wang Kruppel-like Factor 4 (KLF4) Represses Histidine Decarboxylase Gene Expression through an Upstream Sp1 Site and Downstream Gastrin Responsive Elements J. Biol. Chem., March 5, 2004; 279(10): 8684 - 8693. [Abstract] [Full Text] [PDF]

				G. Wang, A. B. Leiter, E. W. Englander, and G. H. Greeley Jr. Insulin-Like Growth Factor I Increases Rat Peptide YY Promoter Activity through Sp1 Binding Sites Endocrinology, February 1, 2004; 145(2): 659 - 666. [Abstract] [Full Text] [PDF]

				R. Raychowdhury, G. Schafer, J. Fleming, S. Rosewicz, B. Wiedenmann, T. C. Wang, and M. Hocker Interaction of Early Growth Response Protein 1 (Egr-1), Specificity Protein 1 (Sp1), and Cyclic Adenosine 3'5'-Monophosphate Response Element Binding Protein (CREB) at a Proximal Response Element Is Critical for Gastrin-Dependent Activation of the Chromogranin A Promoter Mol. Endocrinol., December 1, 2002; 16(12): 2802 - 2818. [Abstract] [Full Text] [PDF]