Keywords
How to Cite
Abstract
The enteric nervous system (ENS), communicates with the central nervous system (CNS) in a dynamic and complex fashion, through different pathways forming a bidimensional axis. This balance depends on several factors, between these systems and serotonin synthesis (5 HT). The gut synthesizes about 90% of the serotonin in our body and participates in various functions such as physiological control of the energy balance and maintenance of intestinal homeostasis. However, does serotonin that is synthesized in the gut have any impact on the brain and gut? Knowledge of the relationship between the gut-brain axis and participation of the serotonin system in the control of food intake and satiety in obesity is of great interest and importance, a fascinating and growing field. Objective: To describe and analyze interactions between the Central Nervous System (CNS) and the Enteric Nervous System (ENS), related to the serotonergic mechanism in obesity. Method: A bibliographic review included data from 134 scientific articles published between 2014 and 2021 in the PubMed, SciELO, LILACS, PsycINFO and ISI Web of Knowledge databases. Results and Conclusions: Interactions between the CNS and the ENS show gastrointestinal sensory motor functions. The gut produces around 90% of serotonin in our body. However, serotonin exerts approximately 80% of its action within the gut and most of the body’s 5-HT is secreted into the bloodstream, where it is largely and rapidly eliminated by the liver and lungs. CNS serotonergic neurons are independent from ENS serotonergic neurons and enteroendocrine cells. In addition, the blood-brain barrier is impermeable to serotonin. Therefore, serotonin synthesis in the brain is one of the major mechanisms that control hunger and satiety as well as carbohydrate ingestion, some of the contributing factors in the development of obesity. Integrative medicine represents a change in paradigm from a medical view of hermetically closed compartments to an interdisciplinary view between the brain-gut axis and the serotonin mechanism in obesity.
References
ANDERSON, G. M.; STEVENSON, J. M.; COHEN, D. J. Steady-state model for plasma free and platelet serotonin in man. Life Sci. v. 41, p. 1777-1785, 1987.
ATKINSON, W. et al. Altered 5-hydroxytryptamine signaling in patients with constipation-and diarrheapredominant irritable bowel syndrome. Gastroenterology, v. 130, p. 34-43, 2006.
BARBIERS, M. et al. Projections of neurochemically specified neurons in the porcine colon. Histochemistry, v. 103, n. 2, p. 115-126, 1995.
BERTRAND, P. P. Real-time measurement of serotonin release and motility in guinea pig ileum. Journal of Physiology, London, v. 577, n. 2, p. 689-704, 2006.
BERTRAND, P. P.; FURNESS, J. B.; BORNSTEIN, J. C. 5-HT and ATP stimulate the mucosal terminals of some myenteric sensory neurons and cause increases in excitability in a population of sensory neurons. O eixo intestino-cérebro... Arq. Ciênc. Saúde UNIPAR, Umuarama, v. 18, n. 1, p. 33-42, jan./abri. 2014 39 Neurogastroenterology, Freiburg, n. 112, 1999.
BERTHOUD, H. R.; LYNN, P. A.; BLACKSHAW, L. A. Vagal and spinal mechanosensors in the rat stomach and colon have multiple receptive fields. Am. J. Physiol. Regul. Integr. Comp. Physiol. v. 280, p. R1371-R1381, 2001.
BLACKSHAW, L. A.; GRUNDY, D. Effects of 5-hydroxytryptamine on discharge of vagal mucosal afferent fibres from the upper gastrointestinal tract of the ferret. J. Auton. Nerv. Syst. v. 45, p. 41-50, 1993.
BROOKES, S. J. H. Classes of enteric nerve cells in the guinea-pig small intestine. Anat. Rec. v. 262, p. 58-70, 2001.
BUÉNO, L. et al. Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. Gastroenterology, v. 112, p. 1714-1743, 1997.
BÜLBRING, E.; GERSHON, M. D. 5-Hydroxytryptamine participation in the vagal inhibitory innervation of the stomach. J. Physiol. v. 192, p. 823-846, 1967.
CASSUTO, J. et al. 5-Hydroxytryptamine and cholera secretion: Physiological and pharmacological studies in cats and rats. Sand. J. Gastroenterol. v. 17, p. 695-703, 1982.
CAMILLERI, M.; S. B.; SASLOW, A. E.; BHARUCHA, A. Gastrointestinal sensation: Mechanisms and relation to functional gastrointestinal disorders. Gastroenterol. Clin. North. Am. v. 25, p. 247-258, 1996.
CAMILLERI, M. et al. Management of the irritable bowel syndrome. Gastroenterology, v. 120, p. 652-668, 2001. CATAPANI, W. Conceitos atuais em síndrome do intestino irritável. Arq. Med. ABC, v. 29, n. 1, 2004.
CERVERO, F. Sensory innervation of the viscera: peripheral basis of visceral pain. Physiol. Rev. v. 74, p. 95- 138, 1994. CHEN, J. J. et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter (SERT): Abnormal intestinal motility and the expression of cation transporters. J. Neurosci. v. 21, p. 6348-6361, 2001.
CHEMSYNTHESIS. 5-Hydroxytryptamine CAS 50-67-9. Disponível em: http://www.chemsynthesis.com/base/chemical-structure-1513.html. Acesso em: 19 set. 2022.
COATES, M. D. et al. Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse. Neurogastroenterol. Motil. v. 18, p. 464- 471, 2006.
COOK, H. J.; REDDIX, R. A. Neural regulation of intestinal electrolyte transport. In: JOHNSON, L. R. (Ed.). Physiology of the gastrointestinal. 1994.
COOKE, H. J.; SIDHU, M.; WANG, Y-Z. 5-HT activates neural reflexes regulating secretion in the guinea-pig colon. Neurogastroenterol. Motil. v. 9, p. 181-186, 1997.
COSTA, M.; BROOKES, S. J. H.; HENNIG, G. W. Anatomy and physiology of the enteric nervous system. Gut, v. 47, p. iv15–iv19, 2000.
COSTA, M.; BROOKES, S. J. H. The enteric nervous system. Am. J. Gastroenterol. v. 89, p. 125-137, 1994.
COSTA, M.; FURNESS, J. B. The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br. J. Pharmacol. v. 65, p. 237-248, 1979. Neuronal peptides in the intestine. Britssh Medical Bulletin, v. 38, p. 247-252, 1987.
COSTA, M. et al. Neurons with 5-hydroxytryptaminelike immunoreactivity in the enteric nervous system: their visualization and reactions to drug treatment. Neuroscience, v. 7, n. 2, p. 351-363, 1982.
COTE, F. et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc. Natl. Acad. Sci. v. 100, p. 13525- 13530, 2003.
DANTZER, R. et al. Cytokines and sickness behavior. Ann. N. Y. Acad. Sci. v. 840, p. 586-590, 1998. DESAI, K. M. et al. Nitroxergic nerves mediate vagally induced relaxation in the isolated stomach of the guinea pig. Proc. Natl. Acad. Sci. v. 88, p. 11490-11494, 1991.
DOGIEL, A. S. Über den Bau der Ganglien in den Geflechten des Darmes und der Gallenblase dês Menschen und de
DUNLOP, S. P. et al. Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin. Gastroenterol. Hepatol. v. 3, p. 349-357, 2005.
ERSPAMER, V. Occurrence of indolealkylamines in nature. In: ERSPAMER, V. (Ed.). Handbook of experimental pharmacology: 5-hydroxytryptamine and related indolealkylamines. New York: Springer-Verlag, 1966. p. 132-181.
FANBURG, B. L.; LEE, S. L. A new role for an old molecule: serotonin as a mitogen. Am. J. Physiol. v. 272, p. L795-806, 1997.
FERREIRA, L.; GOMES, E. Estudo Sobre a Eficácia do Uso de Inibidores da Recaptação de Norepinefrina e Serotonina no Tratamento da Obesidade.Revista Saúde e Pesquisa 2009: 2(3):363-9.
FORD, A. C. et al. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut, v. 58, p. 367- 378, 2009.
FUJIMIYA, M. et al. Distribution of serotoninimmunoreactive nerve cells and fibers in the rat gastrointestinal tract. Histochemistry And Cell Biology, v. Arq. Ciênc. Saúde UNIPAR, Umuarama, v. 18, n. 1, p. 33-42, jan./abri. 2014 107, n. 2, p.105-114, 1997.
FURNESS, J. B. The enteric nervious system. Austrália: Blackwell Publishing, 2006. Types of neurons in the enteric nervous system. J. Auton. Nerv. Syste. v. 81, p. 87-96, 2000. Types of nerves in the enteric nervous system. Neuroscience, v. 5, n. 1, p. 1-20, 1980.
FURNESS, J. B.; COSTA, M. The enteric nervous system. New York: Churchill Livingstone, 1987.
FURNESS, J. B. et al. Morphologies and projections of defined classes of neurons in the submucosa of the guineapig small intestine. Anat. Rec. v. 272A, p. 475-483, 2003.
FURNESS, J. B.; KUNZE, W. A. A.; CLERC, N. Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses. American Journal Physiology, v. 277, p. 922- 928, 1999.
FURNESS, J. B. et al. Plurichemical transmission and chemical coding of neurons in the digestive tract. Gastroenterology, v. 108, p. 554-563,1995.
GARFIELD, A.S.; HEISLER, L. K. Pharmacological Targeting of the Serotonergic System for the Treatment of Obesity. J Physiol. 2009; 587(1):49-60.
GARFIELD. Garfield AS and Heisler LK.Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol. 2009; 587(1):49-60.
GEBHART, G. F. Pathobiology of visceral pain: molecular mechanisms and therapeutic implications: IV. Visceral afferent contributions to the pathobiology of visceral pain. Am. J. Physiol. v. 278, p. G834-G838, 2000.
GERSHON, M. D. Effect of tetrodotoxin on innervated smooth muscle preparations. Br. J. Pharmacol. Chemother. v. 29, p. 259-279, 1967. 5-HT (serotonin) physiology and related drugs. Curr. Opin. Gastroenterol. v. 16, p. 113-120, 2000.
GERSHON, M. D.; KIRCHGESSNER, A. L. Identification, characterization and projections of intrinsic primary afferent neurones of the submucosal plexus: Activity- induced expression of c-fos immunoreactivity. Journal of the Autonomic Nervous System, v. 33, p. 185-187, 1991.
GERSHON, M. D.; TACK, J. The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders. Gastroenterology, v. 132, p. 397-414, 2007.
GOODMAN, A.; GILMAN, P. As bases farmacológicas da terapêutica. 9. ed. Rio de Janeiro: McGraw-Hill, 1996.
GREEN, T.; DOCKRAY, G. J. Characterization of the peptidergic afferent innervation of the stomach in the rat, mouse, and guinea-pig. Neuroscience, v. 25, p. 181–193, 1988.
GRONSTARD, K. O. et al. The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine. Scand. J. Gastroenterol. v. 20, p. 163-169, 1985.
GROAT, W. C.; KRIER, J. An electrophysiological study of the sacral parasympathetic pathway to the colon of the cat. J. Physiol. v. 260, p. 425-445, 1976. The sacral parasympathetic reflex pathway regulating colonic motility and defaecation in the cat. J. Physiol. v. 276, p. 481-500, 1978.
GRUNDY, D.; BLACKSHAW, L. A.; HILLSLEY, K. Role of 5-hydroxytryptamine in gastrointestinal chemosensitivity. Dig. Dis. Sci. v. 39, n. 12, p. S44-S47, 1994.
GRUNDY, D.; SCRATCHERD, T. Sensory afferents from the gastrointestinal tract. In: SCHULTZ, S. G. Handbook of Physiology: The Gastrointestinal System, Motility and Circulation. Bethesda: American Physiological Society, 1989. p. 593-620.
HALPERT, A. et al. Clinical response to tricyclic antidepressants in functional bowel disorders is not related to dosage. Am. J. Gastroenterol. v. 100, p. 664-671, 2005.
HARA, J. R. et al. Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis. Am. J. Physiol. Gastrointest. Liver Physiol. v. 287, p. G998-G1007, 2004.
HILLSLEY, K.; GRUNDY, D. Sensitivity to 5-hydroxytryptamine in different afferent subpopulations within mesenteric nerves supplying the rat jejunum. J. Physiol. v. 509, p. 717-727, 1998.
HILLSLEY, K.; KIRKUP, A. J.; GRUNDY, D. Direct and indirect actions of 5-hydroxytryptamine on the discharge of mesenteric afferent fibers innervating the rat jejunum. J. Physiol. v. 506, p. 551-561, 1998.
HOLZER, P. et al. Essential role of vagal afferents in the central signalling of a gastric mucosal acid insult. In: KRAMMER, H. J.; SINGER, M. V. Neurogastroenterology. Dordrecht: From the Basics to the Clincs. Kluwer Academic Publishing, 2000. p. 697-707.
HOLZER, P. et al. Inflammation and gut hypersensitivity: peripheral mechanisms. Gastroenterol. v. 14, p. 32-45, 2001.
HOUGHTON, L. A. et al. Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome. Gut, v. 52, p. 663. Arq. Ciênc. Saúde UNIPAR, Umuarama, v. 18, n. 1, p. 33-42, 2014.
HUSSAIN, M. A.; MITRA, K. A. Effect of aging on tryptophan hydroxylase in rat brain: implications on serotonin level. Drug Metabolism and Disposition, v. 28, n. 9, p. 1038-1042, 2000.
JACOBS, B. L.; AZMITIA, E. C. Structure and function of the brain serotonin system. Physiological Reviews, v. 72, p. 165-229, 1992.
JIN, J. G.; FOXX-ORENSTEIN, A. E.; GRIDER, J. R. Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors. J. Pharmacol. Exp. Ther. v. 288, p. 93-97, 1999.
JULIUS, D. et al. Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation. Science, v. 244, p. 1057-1062, 1989.
JUNQUEIRA, L. C. U.; CARNEIRO, J. Histologia básica. 11. ed. Rio de Janeiro: Guanabara Koogan, 2008.
KALL, E.; LINDSTROM, E.; MARTINEZ, V. The serotonin reuptake inhibitor citalopram does not affect colonic sensitivity or compliance in rats. Eur. J. Pharmacol. v. 570, p. 203-211, 2007.
KHALIL, E. M.; DE ANGELIS, J.; ISHII, M.; COLE, P. A. Mechanism-based inhibition of the melatonin rhythm enzyme: pharmacologic exploitation of active site functional plasticity. Proceedings of the National Academy Sciences of the United States of America, v. 96, n. 22, p. 12418-12423, 1999.
KYRLAGKITSIS, I. KARAMANOLIS, D. G. Pathophysiology of Irritable bowel syndrome: The role of brain-gut axis and serotoninergic receptors. Annals of gastroenterology, v. 15, n. 3, p. 248-252, 2002.
KEGG. Enzyme 2.3.1.87. Disponível em: http://www.genome.jp/dbget-bin/www_bget?ec:2.3.1.87. Acesso em: 30 out. 2022.
KIM, M. et al. D-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffin cells. Gastroenterology, v. 121, p. 1400-1406, 2001.
KIM, D. Y.; CAMILLERI, M. Serotonin: a mediator of the brain-gut connection. Am. J. Gastroenterol. v. 95, p. 2698- 2709, 2000.
KIRCHGESSNER, A. L.; LIU, M. T.; GERSHON, M. D. In situ identification and visualization of neurons that mediate enteric and enteropancreatic reflexes. J. Comp. Neurol. v. 371, p. 270-286, 1996.
KIRCHGESSNER, A. L.; TAMIR, H.; GERSHON, M. D. Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity. J. Neurosci. v. 12, p. 235-249, 1992.
KUWAHARA, A.; KUWAHARA, Y.; KADOWAKI, M. Analysis of FK1052, a new potent 5HT3 and 5HT4 receptor dual antagonist of guinea-pig distal colon. Biomed. Res. v. 3, p. 205-210, 1994.
LAM, D. D.; HEISLER, L. K. Serotonin and energy balance: molecular mechanisms and implications for type 2 diabetes. Expert Rev. Mol. Med. v. 9, n. 5, p. 1-24, 2007.
LAM, D. D, PRZYDZIAL, M. J, RIDLEY, S. H, YEO, G. S. H, ROSHFORD, J. J, O’RAHILLY, S, HEISLER, L. K. Serotonin 5-HT2C Receptor Agonist Promotes Hypophagia via Downstream Activation of Melanocortin 4 Receptors.Endocrinology 2008.
LARSSON, M. H. et al. Elevated motility-related transmucosal potential difference in the upper small intestine in the irritable bowel syndrome. Neurogastroenterol. Motil. v. 19, n. 10, p. 812-820, 2007.
LAUFFER, A. Tradução e validação para o português do Brasil do questionário “Patient Assessment Of Upper Gastrointestinal Disorders-Quality Of Life (PAGI-QOL)” em pacientes dispépticos funcionais. 2010. Dissertação (Mestrado em Medicina: Ciências em Gastroenterologia) – Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Porto Alegre, 2010.
LEGAY, C.; SAFFREY, M. J.; BURNSTOCK, G. Coexistence of immunoreactive substance P and serotonin in neurons of the gut. Brain Res. v. 302, p. 379-382, 1984.
LESURTEL, M. et al. Role of serotonin in the hepatogastroIntestinal tract: an old molecule for new perspectives. Cell Mol. Life Sci. v. 65, p. 940-952, 2008.
LEHNINGER, A.; NELSON, D. L.; COX, M. M. Princípios de bioquímica. 6 ed. São Paulo: Artmed, 2006.
LI, Y. et al. Serotonin released from intestinal enterochromaffin cells mediates luminal non-cholecystokinin-stimulated pancreatic secretion in rats. Gastroenterology, v. 118, p. 1197- 1207, 2000.
LI, Y. et al. Hypothalamic regulation of pancreatic secretion is mediated by central cholinergic pathways in the rat. J. Physiol. v. 552, n. 2, p. 571-587, 2003.
LIN, J.; KUNZE, W.; STANIZ, A. Inflammation of mouse jejunum induces long term excitation in DRG neurons projecting to the viscera. Gastroenterology, v. 126A, p. 896, 2004.
MAIER, S. F. et al. The role of the vagus nerve in cytokineto-brain communication. Ann. N. Y. Acad. Sci. v. 840, p. 289-300, 1998.
MANCINI, M.D. Halpern A. Aspectos Fisiológicos do Balanço Energético. Arq Bras Endocrinol Metab. 2002; 46(3):230-248.
MARTINS, A. C. C. L.; SILVA, T. M.; GLORIAM, B. A. Determinação simultânea de precursores de serotonina – triptofano e 5-hidroxitriptofano – em café. Química Nova, v. 33, n. 2, p. 316-320, 2010.
MARTINS, A. C. C. L. Determinação de precursores da serotonina - triptofano e 5-hidroxitriptoffano - em café por clae-par iônico. 2008. 98f. Dissertação (Mestrado em Ciências de Alimentos) - Universidade Federal de Minas Gerais, Belo Horizonte, 2008.
MAS, A.; GUILLAMON, J. M.; TORIJA, M. J.; BELTRAN, G.; CEREZO, A. B.; TRONCOSO, A. M.; GARCIA-PARRILLA, M. C. Bioactive compounds derived from the yeast metabolism of aromatic amino acids during alcoholic fermentation. BioMed Research International, v. 2014, p. 1-7, 2014.
MEARIN, F. et al. Spittling irritable bowel syndrome: from original Rome to Rome II criteria. Am. J. Gastroenterol. v. 99, p. 122-130, 2004.
MELO, S. R. Neuroanatomia: pintar para aprender. São Paulo: Roca, 2010.
MICHL, T. et al. Vagal afferent signaling of a gastric mucosal acid insult to medullary, pontine, thalamic, hypothalamic and limbic, but not cortical, nuclei of the rat brain. Pain, v. 92, p. 19-27, 2001.
MOHAMMAD-ZADEH, L. F.; MOSES, L.; GWALTNEYBRANT, S. M. Serotonin: a review. J. Vet. Pharmacol. Ther. v. 31, n. 3, p. 187-99, 2008.
MORRISSEY, J. J.; WALKER, M. N.; LOVENBERG, W. The absence of tryptophan hydroxylase activity in blood platelets. Proc. Soc. Exp. Biol. Med. v. 154, p. 496-499, 1977.
NADA, O.; TOYOHARA, T. An immunohistochemical study of serotonin-containing nerves in the colon of rats. VEDOVATO et al. 42 Arq. Ciênc. Saúde UNIPAR, Umuarama, v. 18, n. 1, p. 33-42.
NADAL-VICENS, M.; CHYUNG, H. J.; TUNER, J. T. Farmacologia da neurotransmissão serotoninérgica e adrenérgica central. In: GOLAN, D. E.; TASHJIAN, A. H.; ARMSTRONG, E. J.; ARMSTRONG, A. W. Princípios de Farmacologia: a base fisiopatológica da farmacoterapia. 2 ed. Rio de Janeiro: Guanabara Koogan, 2009.
NASCIMENTO JÚNIOR, E. B. Avaliação do papel da 5-hidroxitriptamina (5-HT) no processamento periférico da resposta nociceptiva. 2011. 79 f. Tese (Doutorado em Ciências Farmacêuticas) –Universidade Federal de Minas Gerais, Belo Horizonte, 2011.
NAVES, A.; Paschoal V. Regulação Funcional da Obesidade. Com Scientiae Saúde 2007; 6(1):189-99.
OHMAN, L.; SIMRÉN, M. New insights into the pathogenesis and pathophysiology of irritable bowel syndrome. Digestive and Liver Disease, v. 39, n. 3, p. 201- 215, 2007.
PAN, H.; GERSHON, M. D. Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine. J. Neurosci. v. 20, p. 3295-3309, 2000.
PASSOS, M. C. F.; RAMOS, A. F. P. Patogenia dos distúrbios gastrointestinais funcionais. Gastroenterologia: da patogenia à prática clínica. 2006. p. 21-34.
RANG, H. P.; RITTER, J. M.; FLOWER, R. J.; HENDERSON, G. Farmacologia. 8 ed., Rio de Janeiro: Elsevier, 2016.
RAYBOULD, H. E. Nutrient tasting and signaling mechanisms in the gut: I. Sensing of lipid by the intestinal mucosa. Am. J. Physiol. v. 277, p. G751-G755, 1999.
ROSSI, L.; TIRAPEGUI, J. Implicações do sistema serotoninérgico no exercício físico. Arquivos Brasileiros de Endocrinologia e Metabologia, v. 48, n. 2, p. 227-233, 2004.
SANDERS-BUSH, E. S.; MAYER, S. E. Agonistas e antagonistas dos receptores da 5-hidroxitriptamina (serotonina). In: GOODMAN, A., GILMAN, P. As bases farmacológicas da terapêutica. 9. ed. Rio de Janeiro: Guanabara Koogan, 1996. p. 183, 1998.
SCHWERTZ, I.; BRADESI, S.; MAYER, E. A. Current insights into pathophysiology of irritable bower syndrome. Curr. Gastroenterology Reports, v. 5, p. 331-336, 2003.
SENGUPTA, J. N.; GEBHART, G. F. Gastrointestinal afferent fibers and sensation. In: JOHNSON, L. (Ed.). Physiology of the Gastrointestinal tract. New York: Raven Press, 1994.
SIDHU, M.; COOKE, H. J. Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion. Am. J. Physiol. Gastointest. Liver Physiol. v. 269, p. G346-G351, 1995.
SUGIUAR, T.; BIELEFELDT, K.; GEBHART, G. F. TRPV1 function in mouse colon sensory neurons is enhanced by metabotropic 5-hydroxytryptamine receptor activation. J. Neurosci. v. 24, p. 9521-9530, 2004.
SZURSZEWSKI, J. H.; MILLER, S. M. Physiology of prevertebral ganglia. In: JOHNSON, L. R. Physiology of the gastrointestinal tract. 3. ed. New York: Raven Press, 1994.
TAMIR, H. et al. Human serotonectin: a blood glycoprotein that binds serotonin and is associated with platelets and white blood cells. J. Cell Sci. v. 73, p. 187-206, 1985.
THOMAS, D. P.; VANE, J. R. 5-hydroxytryptamine in the circulation of the dog. Nature, v. 216, p. 335-338, 1967.
TORTORA, G. J.; NIELSEN, M. T. Princípios de anatomia humana. 12 ed., Rio de Janeiro: Guanabara Koogan, 2013.
VAN KUYK, E. M. et al. Defecation problems in children with Hirschsprung´s disease: a biopsychosocial approach. Pediatric Surgery International, New York, v. 16, n. 5, p. 312-316, 2000.
WALTHER, D. J. et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science, v. 299, p. 76, 2003.
WARDELL, C. F.; BORNSTEIN, J. C.; FURNESS, J. B. Projections of 5-hydroxytryptamine- immunoreactive neurons in guinea-pig distal colon. Cell Tissue Res. v. 278, p. 379-387, 1994.
WEISBRODT, N. W. Motility of the large intestine. In: JACOBSON, E.; JOHNSON, L. R.; WEISBRODT, N. W. Gastrointestinal physiology. St Louis: Mosby, 1997.
WINGREN, U. et al. Endoluminal secretin of serotonin and histamine into the small intestine of normal and nematodeinfected rats. Biogenic Amines, v. 5, p. 297-306, 1988.
WOOD, J. D.; ALPERS, D. H.; ANDREWS, P. L. R. Fundamentals of neurogastroenterology. Gut, v. 45, n. 2, p. II6–II16, 1999.
YANG, M. et al. Serotonin stimulates megakaryocytopoiesis via the 5-HT2 receptor. Blood Coagul Fibrinolysis, v. 7, p. 127-133, 1996.
ZHU, J. X. et al. Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat. J. Physiol. v. 530, p. 431-442, 2001.