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Gary M Mawe - One of the best experts on this subject based on the ideXlab platform.

  • serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients
    Gastroenterology, 2010
    Co-Authors: Christophe Faure, Natalie Patey, Cindy Gauthier, Elice M Brooks, Gary M Mawe
    Abstract:

    Background & Aims In adults, irritable bowel syndrome (IBS) and functional dyspepsia (FD) are chronic conditions that often start during childhood. We investigated mucosal serotonin (5-HT) signaling in children with the idea that data from subjects with a shorter history may improve our understanding of underlying pathophysiological mechanisms. Methods Ninety-eight children undergoing gastroscopy or colonoscopy were studied prospectively. Biopsy specimens were evaluated for inflammation, Enterochromaffin Cell numbers, 5-HT content, and messenger RNA (mRNA) levels for the synthetic enzyme, tryptophan hydroxylase 1, and the serotonin transporter (SERT) were assessed by quantitative real-time reverse-transcription polymerase chain reaction. Results Data from 12 children with IBS and 17 with FD were compared with age-matched controls (12 with rectal biopsies and 12 with gastric biopsies) and with subjects with organic disorders. In patients with FD, a small number of immune Cells were observed in the gastric mucosa in half of the patients, but no abnormalities with respect to the 5-HT pathway were identified. In patients with IBS, no differences were detected between patients and controls regarding intraepithelial lymphocytes and CD3+ Cells in the lamina propria although all patients showed at least a slight inflammatory infiltrate. In the IBS samples, higher 5-HT content ( P P P P P Conclusions These results confirm the role of 5-HT signaling in IBS in children and argue against such a role in FD.

  • review article intestinal serotonin signalling in irritable bowel syndrome
    Alimentary Pharmacology & Therapeutics, 2006
    Co-Authors: Gary M Mawe, Matthew Coates, Peter L Moses
    Abstract:

    Alterations in motility, secretion and visceral sensation are hallmarks of irritable bowel syndrome. As all of these aspects of gastrointestinal function involve serotonin signalling between Enterochromaffin Cells and sensory nerve fibres in the mucosal layer of the gut, potential alterations in mucosal serotonin signalling have been explored as a possible mechanism of altered function and sensation in irritable bowel syndrome. Literature related to intestinal serotonin signalling in normal and pathophysiological conditions has been searched and summarized. Elements of serotonin signalling that are altered in irritable bowel syndrome include: Enterochromaffin Cell numbers, serotonin content, tryptophan hydroxylase message levels, 5-hydroxyindoleacedic acid levels, serum serotonin levels and expression of the serotonin-selective reuptake transporter. Both genetic and epigenetic factors could contribute to decreased serotonin-selective reuptake transporter in irritable bowel syndrome. A serotonin-selective reuptake transporter gene promoter polymorphism may cause a genetic predisposition, and inflammatory mediators can induce serotonin-selective reuptake transporter downregulation. While a psychiatric co-morbidity exists with IBS, changes in mucosal serotonin handling support the concept that there is a gastrointestinal component to the aetiology of irritable bowel syndrome. Additional studies will be required to gain a more complete understanding of changes in serotonin signalling that are occurring, their cause and effect relationship, and which of these changes have pathophysiological consequences.

  • Enterochromaffin Cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction
    Neurogastroenterology and Motility, 2005
    Co-Authors: Johanna Wheatcroft, Derek Wakelin, Adrian Smith, C R Mahoney, Gary M Mawe, Robin C Spiller
    Abstract:

    Patients with postinfective irritable bowel syndrome and Trichinella spiralis-infected mice share many features including visceral hypersensitivity and disordered motility. We assessed Enterochromaffin (EC) numbers and serotonin transporter (SERT) using National Institute of Health (NIH) female mice studied for up to 56 days post-T. spiralis infection. The effects of steroid treatment and the T-Cell dependence of the observed responses were assessed by infection of hydrocortisone-treated or T-Cell receptor knock out [TCR (betaxdelta) KO] animals. Enterochromaffin Cell density in uninfected animals increased from duodenum 10.0 Cells mm-2 (5.9-41.0) to colon 61.8. (46.3-162) Cells mm-2 P<0.0001. Infection increased duodenal and jejunal counts which rose to 37.3 (22-57.7) Cells mm-2 and 50.6 (7-110.8) Cells mm-2, respectively, at day 14. Infection significantly reduced jejunal SERT expression, with luminance values falling from 61.0 (45.1-98.3) to a nadir of 11.6 (0-36.0) units at day 9, P<0.001. Specific deficiencies in all T Cells reduced EC hyperplasia and abrogated infection-induced mastocytosis. Thus infection induced inflammation increases EC numbers, as has been reported in PI-IBS, and reduces SERT. This may increase mucosal 5HT availability and contribute to the clinical presentation of PI-IBS.

  • molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome
    Gastroenterology, 2004
    Co-Authors: Matthew Coates, David R. Linden, Michael D. Gershon, Christine R Mahoney, Joanna E Sampson, Jason Chen, Hagen Blaszyk, Michael D Crowell, Keith A Sharkey, Gary M Mawe
    Abstract:

    Background & Aims: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from Enterochromaffin Cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. Methods: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. Results: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The Enterochromaffin Cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. Conclusions: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.

Waliul I Khan - One of the best experts on this subject based on the ideXlab platform.

  • il 13 mediated immunological control of Enterochromaffin Cell hyperplasia and serotonin production in the gut
    Mucosal Immunology, 2013
    Co-Authors: Marcus Manocha, Huaqing Wang, Waliul I Khan, Mohammad Sharif Shajib, Mizanur Rahman, P Rengasamy, Milena Bogunovic, Manel Jordana, Lloyd Mayer
    Abstract:

    Enterochromaffin (EC) Cells in the gastrointestinal (GI) mucosa are the main source of serotonin (5-hydroxytryptamine (5-HT)) in the body. 5-HT is implicated in the pathophysiology of many GI disorders including functional and inflammatory bowel disorders. Herein we studied the role of interleukin 13 (IL-13) in EC Cell biology by utilizing IL-13-deficient (IL-13-/-) mice and BON Cells (a model for human EC Cells). The numbers of EC Cells and 5-HT amount were significantly lower in enteric parasite, Trichuris muris-infected IL-13-/- mice compared with the wild-type mice. This was accompanied with increased parasite burden in IL-13-/- mice. Treatment of naive and infected IL-13-/- mice with IL-13 increased EC Cell numbers and 5-HT amount. BON Cells expressed IL-13 receptor and in response to IL-13 produced more 5-HT. These results provide novel information on IL-13-mediated immunological control of 5-HT in the gut, which may ultimately lead to improved therapeutic opportunities in various GI disorders.

  • Enterochromaffin Cell and 5 hydroxytryptamine responses to the same infectious agent differ in th1 and th2 dominant environments
    Gut, 2007
    Co-Authors: Yasuaki Motomura, Jeaneric Ghia, Huaqing Wang, Hirotada Akiho, Rami T Elsharkawy, Matthew Collins, Yonghong Wan, John Mclaughlin, Waliul I Khan
    Abstract:

    Background/aim: 5-Hydroxytryptamine (5-HT) released from Enterochromaffin Cells influences intestinal homeostasis by altering gut physiology and is implicated in the pathophysiology of various gut disorders. The mechanisms regulating 5-HT production in the gut remain unclear. This study investigated the T helper (Th) 1/Th2-based immunoregulation of Enterochromaffin Cell function and 5-HT production in a model of enteric infection. Methods and results: Trichuris muris -infected AKR (susceptible to infection and generates Th1 response), BALB/c (resistant to infection and generates Th2 response), Stat4-deficient (impaired in Th1 response) and Stat6-deficient (impaired in Th2 response) mice were investigated to assess Enterochromaffin Cells, 5-HT and cytokines. In association with the generation of a Th2 response we observed higher Enterochromaffin Cell numbers and 5-HT content in the colon of BALB/c mice compared with AKR mice. Numbers of Enterochromaffin Cells and amount of 5-HT were significantly lower in Stat6-deficient mice after infection compared with Stat4-deficient mice. In addition, Enterochromaffin Cell numbers and 5-HT content were significantly higher after reconstitution of severe combined immunodeficient mice with in-vitro polarised Th2 Cells. Conclusion: The study demonstrated that Enterochromaffin Cell and 5-HT responses to the same infectious agent are influenced by Th1 or Th2 cytokine predominance and suggests that the immunological profile of the inflammatory response is important in the regulation of Enterochromaffin Cell biology in the gut. In addition to new data on Enterochromaffin Cell function in enteric infection and inflammation, this study provides important information on the immuno–endocrine axis in the gut, which may ultimately lead to improved strategies against gut disorders.

  • cd4 t Cell mediated immunological control of Enterochromaffin Cell hyperplasia and 5 hydroxytryptamine production in enteric infection
    Gut, 2007
    Co-Authors: Huaqing Wang, Yasuaki Motomura, Rami T Elsharkawy, John Mclaughlin, Justin Thomas Steeds, Yikang Deng, Monica Vermagandhu, Richard K Grencis, Waliul I Khan
    Abstract:

    Background & Aims: Enterochromaffin (EC) Cells are dispersed throughout the gastrointestinal (GI) mucosa and are the main source of 5-hydroxytryptamine (5-HT) in the gut. 5-HT has been implicated in the pathophysiology of a number of GI disorders but the mechanisms regulating the 5-HT production in the gut are unknown. This study investigated the role of CD4 + T Cells in 5-HT production using a model of enteric parasitic infection. Methods & Results: Severe combined immune deficiency (SCID) mice and their wild-type controls were infected with nematode, Trichuris muris and euthanized on various days post-infection to study colonic EC Cells and 5-HT. The number of EC Cells and 5-HT were significantly higher in infected wild-type mice compared to non-infected mice. EC Cells numbers and 5-HT amount were significantly lower in SCID mice after infection as compared to wild-type mice. Numbers of EC Cells and 5-HT amount significantly increased following reconstitution of SCID mice with CD4 + T Cells from infected mice and this was accompanied by an up-regulation of colonic CD3 + T Cells and Th2 cytokines. Laser capture microdissection based molecular and immunofluorescence techniques revealed the presence of the IL-13 receptor a1-chain on EC Cell. Conclusion: These results demonstrate an important immuno-endocrine axis in the gut, where secretory products from CD4 + T Cells interact with EC Cells to enhance 5-HT production in the gut via Th2 based mechanisms. These results demonstrate new insights into the mechanisms of gut function which may ultimately lead to improved therapeutic strategies in GI functional and inflammatory disorders.

Zhaoxiang Bian - One of the best experts on this subject based on the ideXlab platform.

  • Enterochromaffin Cell hyperplasia in the gut factors mechanism and therapeutic clues
    Life Sciences, 2019
    Co-Authors: Hongyan Qin, Hoi Leong Xavier Wong, Kaihong Zang, Zhaoxiang Bian
    Abstract:

    Enterochromaffin (EC) Cell is the main Cell type that responsible for 5-hydroxytryptamine (5-HT) synthesis, storage and release of the gut. Intestinal 5-HT play a key role in visceral sensation, intestinal motility and permeability, EC Cell hyperplasia and increased 5-HT bioavailability in the gut have been found to be involved in the symptoms generation of irritable bowel syndrome and inflammatory bowel disease. EC Cells originate from intestinal stem Cells, the interaction between proliferation and differentiation signals on intestinal stem Cells enable EC Cell number to be regulated in a normal level. This review focuses on the impact factors, pathogenesis mechanisms, and therapeutic clues for intestinal EC Cells hyperplasia, and showed that EC Cell hyperplasia was observed under the condition of physiological stress, intestinal infection or intestinal inflammation, the disordered proliferation and/or differentiation of intestinal stem Cells as well as their progenitor Cells all contribute to the pathogenesis of intestinal EC Cell hyperplasia. The altered intestinal niche, i.e. increased corticotrophin releasing factor (CRF) signal, elevated nerve growth factor (NGF) signal, and Th2-dominant cytokines production, has been found to have close correlation with intestinal EC Cell hyperplasia. Currently, CRF receptor antagonist, nuclear factor-κB inhibitor, and NGF receptor neutralizing antibody have been proved useful to attenuate intestinal EC Cell hyperplasia, which may provide a promising clue for the therapeutic strategy in EC Cell hyperplasia related diseases.

  • visceral hypersensitivity induced by activation of transient receptor potential vanilloid type 1 is mediated through the serotonin pathway in rat colon
    European Journal of Pharmacology, 2010
    Co-Authors: Shengda Qi, Hongxi Xu, Joseph J Y Sung, Zhaoxiang Bian
    Abstract:

    Abstract This study aimed to clarify the relationship between TRPV1 activation-induced visceral pain and the serotonin pathway in the colon of rats. The effects of para-chlorophenylalanine (pCPA) on visceral pain threshold pressure were assessed in capsaicin -induced visceral pain of rats. The expression of TRPV1 in the colon was examined by immunohistochemistry and Western blot analysis, and TRPV1 excitability in dorsal root ganglion (DRG) neurons was examined by whole-Cell patch-clamp recording in pCPA-treated rats. Calcineurin and Ca2+-calmodulin-dependent kinase II (CaMKII), the important proteins in maintaining TRPV1 function in the colon, were also tested by Western blot analysis and immunofluorescence staining. Results showed that pCPA significantly increased the capsaicin-induced visceral pain threshold by 2.3-fold, and the enhanced visceral pain threshold corresponded with decreased 5-HT content (58% depleted) and Enterochromaffin Cell number (80% reduced). The reduced excitability of TRPV1 in DRG neurons, instead of changed TRPV1 expression, is responsible for the enhanced visceral pain threshold in 5-HT-depleted rats, and the mechanism may be related to the decreased expression of pCaMKII. These results indicate that visceral hypersensitivity induced by TRPV1 activation is modulated through 5-HT pathways and the attenuated function of TRPV1 and decreased protein expression of pCaMKII may play an important role in capsaicin-induced TRPV1 desensitization under 5-HT-depleted condition. The important role of TRPV1 and 5-HT in generating and maintaining visceral hypersensitivity may provide insights for the treatment of visceral hypersensitivity.

Andrew A Lackner - One of the best experts on this subject based on the ideXlab platform.

  • proximity between 5 ht secreting enteroendocrine Cells and lymphocytes in the gut mucosa of rhesus macaques macaca mulatta is suggestive of a role for Enterochromaffin Cell 5 ht in mucosal immunity
    Journal of Neuroimmunology, 2004
    Co-Authors: Guibo Yang, Andrew A Lackner
    Abstract:

    The involvement of serotonin (5-hydroxytryptamine; 5-HT) in immunoregulation has been well documented. Gut mucosa is a large reservoir of 5-HT most of which is attributed to gut endocrine Cells. In this study, we examined the anatomical relationship among 5-HT immunoreactive Cells and T and B lymphocytes in the gut mucosa of rhesus monkeys (Macaca mulatta). 5-HT, CD3 and CD20 immunoreactive Cells were immunofluorescently labeled and visualized by confocal microscopy. 5-HT immunoreactive Cells were primarily found within the epithelium of the intestine and were present at all levels of the gastrointestinal tract. Many 5-HT immunoreactive Cells were in contact with, or very close proximity to CD3 + and CD20 + lymphocytes. These results provide morphological evidence to suggest interactions between 5-HT secreting enteroendocrine Cells and lymphocytes in the gut mucosa. This further supports a possible role of 5-HT in mucosal immune responses. D 2003 Elsevier B.V. All rights reserved.

  • proximity between 5 ht secreting enteroendocrine Cells and lymphocytes in the gut mucosa of rhesus macaques macaca mulatta is suggestive of a role for Enterochromaffin Cell 5 ht in mucosal immunity
    Journal of Neuroimmunology, 2004
    Co-Authors: Guibo Yang, Andrew A Lackner
    Abstract:

    The involvement of serotonin (5-hydroxytryptamine; 5-HT) in immunoregulation has been well documented. Gut mucosa is a large reservoir of 5-HT most of which is attributed to gut endocrine Cells. In this study, we examined the anatomical relationship among 5-HT immunoreactive Cells and T and B lymphocytes in the gut mucosa of rhesus monkeys (Macaca mulatta). 5-HT, CD3 and CD20 immunoreactive Cells were immunofluorescently labeled and visualized by confocal microscopy. 5-HT immunoreactive Cells were primarily found within the epithelium of the intestine and were present at all levels of the gastrointestinal tract. Many 5-HT immunoreactive Cells were in contact with, or very close proximity to CD3(+) and CD20(+) lymphocytes. These results provide morphological evidence to suggest interactions between 5-HT secreting enteroendocrine Cells and lymphocytes in the gut mucosa. This further supports a possible role of 5-HT in mucosal immune responses.

Mark Kidd - One of the best experts on this subject based on the ideXlab platform.

  • the role of mechanical forces and adenosine in the regulation of intestinal Enterochromaffin Cell serotonin secretion
    American Journal of Physiology-gastrointestinal and Liver Physiology, 2012
    Co-Authors: Alexander L Chin, Bjorn I Gustafsson, Roswitha Pfragner, Irvin M Modlin, Bernhard Svejda, Atle Van Beelen Granlund, Arne K Sandvik, Andrew T Timberlake, Bauer E Sumpio, Mark Kidd
    Abstract:

    Enterochromaffin (EC) Cells of the diffuse neuroendocrine Cell system secrete serotonin (5-HT) with activation of gut motility, secretion, and pain. These Cells express adenosine (ADORA) receptors and are considered to function as mechanosensors. Physiological pathways mediating mechanosensitivity and adenosine responsiveness remain to be fully elucidated, as do their roles in inflammatory bowel disease (IBD) and neoplasia. Pure (98–99%) FACS-sorted normal and IBD human EC Cells and neoplastic EC Cells (KRJ-I) were studied. IBD-EC Cells and KRJ-I overexpressed ADORA2B. NECA, a general ADORA receptor agonist, stimulated, whereas the A2B receptor antagonist MRS1754 inhibited, 5-HT release (EC50 = 1.8 × 10−6 M; IC50 = 3.7 × 10−8 M), which was associated with corresponding alterations in intraCellular cAMP levels and pCREB (Ser133). Mechanical stimulation using a rhythmic flex model induced transcription and activation of Tph1 (tryptophan hydroxylase) and VMAT1 (vesicular monoamine transporter 1) and the release of 5-HT, which could be inhibited by MRS1754 and amplified by NECA. Secretion was also inhibited by H-89 (PKA inhibitor) while Tph1 and VMAT1 transcription was regulated by PKA/MAPK and PI3K-mediated signaling. Normal and IBD-EC Cells also responded to NECA and mechanical stimulation with PKA activation, cAMP production, and 5-HT release, effects reversible by MRS1754. EC Cells express stimulatory ADORA2B, and rhythmic stretch induces A2B activation, PKA/MAPK/IP3-dependent transcription, and PKA-dependent secretion of 5-HT synthesis and secretion. Receptor expression is amplified in IBD and neoplasia, and 5-HT release is increased. Determination of factors that regulate EC Cell function are necessary for understanding its role as a mechanosensory Cell and to facilitate the development of agents that can selectively target Cell function in EC Cell-associated disease.

  • krj i and bon Cell lines defining an appropriate Enterochromaffin Cell neuroendocrine tumor model
    Neuroendocrinology, 2009
    Co-Authors: Zakiyaluna Siddique, Bjorn I Gustafsson, Ignat Drozdov, Jared Floch, Kamilla Stunes, Roswitha Pfragner, Mark Kidd, Irvin M Modlin
    Abstract:

    Background: Neuroendocrine tumors (NETs) of the gastrointestinal (GI) system are increasing in incidence with minimal improvement in prognosis. Although the Cell of origin has been

  • from leningrad to london the saga of kulchitsky and the legacy of the Enterochromaffin Cell
    Neuroendocrinology, 2009
    Co-Authors: Ignat Drozdov, Mark Kidd, Irvin M Modlin, Viktor V Goloubinov
    Abstract:

    By the end of the 19th century, the subject of internal secretion and the consequences of its perturbations had been explored in considerable depth but with little clear understanding. Despite the ana

  • small bowel carcinoid Enterochromaffin Cell neoplasia exhibits transforming growth factor β1 mediated regulatory abnormalities including up regulation of c myc and mta1
    Cancer, 2007
    Co-Authors: Mark Kidd, Roswitha Pfragner, Irvin M Modlin, Geeta N Eick, Manish C Champaneria, Anthony K Chan, Robert L Camp, Shrikant Mane
    Abstract:

    BACKGROUND. Although it is known that small intestinal carcinoids are derived from Enterochromaffin (EC) Cells, these Cells remain poorly characterized and little is known of the growth regulatory mechanisms of these neuroendocrine Cells. Down-regulation or loss of the transforming growth factor-β1 (TGFβ1) cytostatic program and activation of TGFβ-mediated transcriptional networks is associated with uncontrolled growth and metastasis in other neural tumors, glioblastomas. Whether this phenomenon is common to small intestinal carcinoid tumors was investigated. METHODS. The effects of TGFβ1 on cultured normal EC Cells (isolated by FACS sorting) and the neoplastic EC Cell line, KRJ-I, was assessed using the MTT assay. The TGFβRII transcript and protein were identified in tumor Cells and the effects of TGFβ1 on SMAD2 phosphorylation and nuclear translocation quantified. The time-dependent response of SMAD4, SMAD7, c-Myc, and P21WAF1/CIP1 protein expression and c-Myc and p21WAF1/CIP1 transcript was measured in response to TGFβ1 and the transcript expression of candidate downstream targets, MTA1 and E-cadherin, were assessed. RESULTS. TGFβ1 inhibited normal EC Cell proliferation (IC50 = 17 pM) but stimulated neoplastic EC Cell proliferation (EC50 = 22 pM). In tumor Cells, significantly decreased transcript (P 16%, P 21% (P < .05) and ≈40% (P < .002). TGFβ1 (1 ng/mL) also decreased p21WAF1/CIP1 transcript by 60% (P < .001) and protein that was undetectable at 24 hours. Expression of the downstream targets of the c-Myc pathway, MTA1, was increased (20%) and E-cadherin decreased (30%). CONCLUSIONS. The neoplastic EC Cell is characterized by loss of TGFβ-1-mediated growth inhibition and, similar to glioblastomas, utilizes the TGFβ system to induce gene responses associated with growth promotion (c-Myc and the ERK pathway), invasion (E-cadherin), and metastasis (MTA1). Cancer 2007. © 2007 American Cancer Society.

  • further delineation of the continuous human neoplastic Enterochromaffin Cell line krj i and the inhibitory effects of lanreotide and rapamycin
    Journal of Molecular Endocrinology, 2007
    Co-Authors: Mark Kidd, Roswitha Pfragner, Irvin M Modlin, Geeta N Eick, Manish C Champaneria, John R Murren
    Abstract:

    Small intestinal carcinoids (SICs) are the most prevalent gastrointestinal carcinoid and characterized by local invasion metastasis and protean symptomatology. The proliferative and secretory regulation of the Cell of origin, the Enterochromaffin (EC) Cell has not been characterized. The absence of either a pure preparation of normal EC Cells or human EC carcinoid Cell lines has hindered the development of therapeutic agents. We therefore further characterized the neoplastic SIC Cell line, KRJ-I by assessing its secretory (serotonin (5-HT)) and proliferative responses and defining its log growth phase transcriptome. Electron microscopy demonstrated oval, lobulated nuclei and substance P, and 5HT-positive cytoplasmic vesicles. RT-PCR detected transcripts for chromogranin A (CHGA), VMAT1 (SLC18A1), tryptophan hydroxylase (TPH1), substance P (TAC1), guanylin (GUCA2A), and SERT (SLC6A4). By immunohistochemistry, all Cells were positive for CHGA, SERT, VMAT1, and TPH1. Transcriptome analysis (Affymetrix U133 Plus chips) identified somatostatin SSTR2/3, adrenergic a1C and b1, dopamine D2, nicotinic-type cholinergic A5, A6, B1, muscarinic acetylcholine M4, and 5-HT-2A receptors. The presence of transcripts for SSTR1, SSTR2, and SSTR3 receptors was confirmed by RT-PCR and sequencing. Isoproterenol (ISO) resulted in a dose-dependent increase in intraCellular cAMP (EC50Z340 nM) and 5-HT (EC50Z81 nM) which was completely inhibited by the cAMP antagonist 2 0 ,5 0 -dideoxyadenosine (10 mM). Preincubation with a SSTR agonist, lanreotide, inhibited Ip-stimulated 5-HT secretion (IC50Z420 nM). Both lanreotide (10 nM) and rapamycin (50 nM) inhibited proliferation (20G12 and 35G5% respectively) in serum-free medium whereas gefitinib (1 nM‐10 mM) inhibited proliferation at micromolar concentrations. KRJ-I is a neoplastic EC Cell line that can be used as an in vitro model of SICs as it will allow elucidation and clarification of the secretory and proliferative mechanism(s) of neoplastic EC Cells and the molecular signatures that characterize each of these responses.