QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (142) Citing Articles via Google Scholar Google Scholar Articles by Chen, J. J. Articles by Gershon, M. D. Search for Related Content PubMed PubMed Citation Articles by Chen, J. J. Articles by Gershon, M. D.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 15, 2001, 21(16):6348-6361

Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters

Jason J. Chen¹, Zhishan Li¹, Hui Pan¹, Dennis L. Murphy², Hadassah Tamir^{1, 3}, Hermann Koepsell⁴, and Michael D. Gershon¹

¹ Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, ² Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892, ³ New York State Psychiatric Institute, New York, New York 10032, and ⁴ Anatomisches Institut der Bayerischen Julius-Maximilians-Universitat, D-97070 Würzburg, Germany

The enteric serotonin reuptake transporter (SERT) has been proposed to play a critical role in serotonergic neurotransmission and in the initiation of peristaltic and secretory reflexes. We analyzed potential compensatory mechanisms and enteric function in the bowels of mice with a targeted deletion of SERT. The guts of these animals were found to lack mRNA encoding SERT; moreover, high-affinity uptake of 5-HT into epithelial cells, mast cells, and enteric neurons was present in the SERT +/+ bowel but absent in the SERT / bowel. However, both the SERT +/+ gut and the / gut expressed molecules capable of transporting 5-HT, but with affinities and selectivity much lower than those of SERT. These included the dopamine transporter (DAT) and polyspecific organic cation transporters OCT-1 and OCT-3. DAT and OCT immunoreactivities were present in both the submucosal and myenteric plexuses, and the OCTs were also located in the mucosal epithelium. 5-HT was found in all of its normal sites in the SERT / bowel, which contained mRNA encoding tryptophan hydroxylase, but no 5-HT was present in the blood of SERT / animals. Stool water and colon motility were increased in most SERT / animals; however, the increase in motility (diarrhea) occasionally alternated irregularly with decreased motility (constipation). The watery diarrhea is probably attributable to the potentiation of serotonergic signaling in SERT / mice, whereas the transient constipation may be caused by episodes of enhanced 5-HT release leading to 5-HT receptor desensitization.

Key words: serotonin reuptake transporter; enteric nervous system; gastrointestinal motility; organic cation transporters; dopamine transporter; SERT knock-out mice

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/21166348-14$05.00/0

This article has been cited by other articles:

				C. Mendoza, N. Matheus, R. Iceta, J. E. Mesonero, and A. I. Alcalde Lipopolysaccharide induces alteration of serotonin transporter in human intestinal epithelial cells Innate Immunity, August 1, 2009; 15(4): 243 - 250. [Abstract] [PDF]

				J. M. Cyphert, M. Kovarova, I. C. Allen, J. M. Hartney, D. L. Murphy, J. Wess, and B. H. Koller Cooperation between Mast Cells and Neurons Is Essential for Antigen-Mediated Bronchoconstriction J. Immunol., June 15, 2009; 182(12): 7430 - 7439. [Abstract] [Full Text] [PDF]

				S. C. Bischoff, R. Mailer, O. Pabst, G. Weier, W. Sedlik, Z. Li, J. J. Chen, D. L. Murphy, and M. D. Gershon Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G685 - G695. [Abstract] [Full Text] [PDF]

				K. B. Neal, L. J. Parry, and J. C. Bornstein Strain-specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice J. Physiol., February 1, 2009; 587(3): 567 - 586. [Abstract] [Full Text] [PDF]

				N. L. Baganz, R. E. Horton, A. S. Calderon, W. A. Owens, J. L. Munn, L. T. Watts, N. Koldzic-Zivanovic, N. A. Jeske, W. Koek, G. M. Toney, et al. Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice PNAS, December 2, 2008; 105(48): 18976 - 18981. [Abstract] [Full Text] [PDF]

				A. E. Linder, J. Diaz, W. Ni, T. Szasz, R. Burnett, and S. W. Watts Vascular reactivity, 5-HT uptake, and blood pressure in the serotonin transporter knockout rat Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1745 - H1752. [Abstract] [Full Text] [PDF]

				R. K. Gill, N. Pant, S. Saksena, A. Singla, T. M. Nazir, L. Vohwinkel, J. R. Turner, J. Goldstein, W. A. Alrefai, and P. K. Dudeja Function, expression, and characterization of the serotonin transporter in the native human intestine Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G254 - G262. [Abstract] [Full Text] [PDF]

				B.-S. Feng, S.-H. He, P.-Y. Zheng, L. Wu, and P.-C. Yang Mast Cells Play a Crucial Role in Staphylococcus aureus Peptidoglycan-Induced Diarrhea Am. J. Pathol., August 1, 2007; 171(2): 537 - 547. [Abstract] [Full Text] [PDF]

				X.-Z. Hu, A. J. Rush, D. Charney, A. F. Wilson, A. J. M. Sorant, G. J. Papanicolaou, M. Fava, M. H. Trivedi, S. R. Wisniewski, G. Laje, et al. Association Between a Functional Serotonin Transporter Promoter Polymorphism and Citalopram Treatment in Adult Outpatients With Major Depression Arch Gen Psychiatry, July 1, 2007; 64(7): 783 - 792. [Abstract] [Full Text] [PDF]

				C Altamura, M. Dell'Acqua, R Moessner, D. Murphy, K. Lesch, and A. M. Persico Altered Neocortical Cell Density and Layer Thickness in Serotonin Transporter Knockout Mice: A Quantitation Study Cereb Cortex, June 1, 2007; 17(6): 1394 - 1401. [Abstract] [Full Text] [PDF]

				K. F. Foley, C. Pantano, A. Ciolino, and G. M. Mawe IFN-{gamma} and TNF-{alpha} decrease serotonin transporter function and expression in Caco2 cells Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G779 - G784. [Abstract] [Full Text] [PDF]

				F. Cote, C. Fligny, E. Bayard, J.-M. Launay, M. D. Gershon, J. Mallet, and G. Vodjdani From the Cover: Maternal serotonin is crucial for murine embryonic development PNAS, January 2, 2007; 104(1): 329 - 334. [Abstract] [Full Text] [PDF]

				P. P. Bertrand Real-time measurement of serotonin release and motility in guinea pig ileum J. Physiol., December 1, 2006; 577(2): 689 - 704. [Abstract] [Full Text] [PDF]

				W. Ni, K. Lookingland, and S. W. Watts Response to Blood Pressure in Mutant Rats Lacking the 5-Hydroxytryptamine Transporter Hypertension, December 1, 2006; 48(6): e117 - e117. [Full Text] [PDF]

				J. P. Walterscheid, D. X. Nghiem, N. Kazimi, L. K. Nutt, D. J. McConkey, M. Norval, and S. E. Ullrich Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor PNAS, November 14, 2006; 103(46): 17420 - 17425. [Abstract] [Full Text] [PDF]

				W. Ni, K. Lookingland, and S. W. Watts Arterial 5-Hydroxytryptamine Transporter Function Is Impaired in Deoxycorticosterone Acetate and N{omega}-Nitro-L-Arginine But Not Spontaneously Hypertensive Rats Hypertension, July 1, 2006; 48(1): 134 - 140. [Abstract] [Full Text] [PDF]

				Z. S. Li, C. Schmauss, A. Cuenca, E. Ratcliffe, and M. D. Gershon Physiological modulation of intestinal motility by enteric dopaminergic neurons and the D2 receptor: analysis of dopamine receptor expression, location, development, and function in wild-type and knock-out mice. J. Neurosci., March 8, 2006; 26(10): 2798 - 2807. [Abstract] [Full Text] [PDF]

				J. R. Grider Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserod Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G319 - G327. [Abstract] [Full Text] [PDF]

				P. Amireault and F. Dube Serotonin and Its Antidepressant-Sensitive Transport in Mouse Cumulus-Oocyte Complexes and Early Embryos Biol Reprod, August 1, 2005; 73(2): 358 - 365. [Abstract] [Full Text] [PDF]

				D. E. Baker Rationale for using serotonergic agents to treat irritable bowel syndrome Am. J. Health Syst. Pharm., April 1, 2005; 62(7): 700 - 711. [Abstract] [Full Text] [PDF]

				S. J. Warden, A. G. Robling, M. S. Sanders, M. M. Bliziotes, and C. H. Turner Inhibition of the Serotonin (5-Hydroxytryptamine) Transporter Reduces Bone Accrual during Growth Endocrinology, February 1, 2005; 146(2): 685 - 693. [Abstract] [Full Text] [PDF]

				J. R. O'Hara, W. Ho, D. R. Linden, G. M. Mawe, and K. A. Sharkey Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis Am J Physiol Gastrointest Liver Physiol, November 1, 2004; 287(5): G998 - G1007. [Abstract] [Full Text] [PDF]

				M Camilleri Is there a SERT-ain association with IBS? Gut, October 1, 2004; 53(10): 1396 - 1399. [Full Text] [PDF]

				A Yeo, P Boyd, S Lumsden, T Saunders, A Handley, M Stubbins, A Knaggs, S Asquith, I Taylor, B Bahari, et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women Gut, October 1, 2004; 53(10): 1452 - 1458. [Abstract] [Full Text] [PDF]

				F De Ponti Pharmacology of serotonin: what a clinician should know Gut, October 1, 2004; 53(10): 1520 - 1535. [Full Text] [PDF]

				H J Kim, M Camilleri, P J Carlson, F Cremonini, I Ferber, D Stephens, S McKinzie, A R Zinsmeister, and R Urrutia Association of distinct {alpha}2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders Gut, June 1, 2004; 53(6): 829 - 837. [Abstract] [Full Text] [PDF]

				D. L. Murphy, A. Lerner, G. Rudnick, and K.-P. Lesch Serotonin Transporter: Gene, Genetic Disorders, and Pharmacogenetics Mol. Interv., April 1, 2004; 4(2): 109 - 123. [Abstract] [Full Text] [PDF]

				Z. S. Li, T. D. Pham, H. Tamir, J. J. Chen, and M. D. Gershon Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation J. Neurosci., February 11, 2004; 24(6): 1330 - 1339. [Abstract] [Full Text] [PDF]

				F. Martel, R. Monteiro, and C. Lemos Uptake of Serotonin at the Apical and Basolateral Membranes of Human Intestinal Epithelial (Caco-2) Cells Occurs through the Neuronal Serotonin Transporter (SERT) J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 355 - 362. [Abstract] [Full Text] [PDF]

				D. R. Linden, J.-X. Chen, M. D. Gershon, K. A. Sharkey, and G. M. Mawe Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G207 - G216. [Abstract] [Full Text] [PDF]

				O. A. Tjurmina, I. Armando, J. M. Saavedra, D. S. Goldstein, and D. L. Murphy Exaggerated Adrenomedullary Response to Immobilization in Mice with Targeted Disruption of the Serotonin Transporter Gene Endocrinology, December 1, 2002; 143(12): 4520 - 4526. [Abstract] [Full Text] [PDF]

				M.-T. Liu, S. Rayport, Y. Jiang, D. L. Murphy, and M. D. Gershon Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1398 - G1411. [Abstract] [Full Text] [PDF]

				R. D. Blakely Physiological Genomics of Antidepressant Targets: Keeping the Periphery in Mind J. Neurosci., November 1, 2001; 21(21): 8319 - 8323. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help