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

Abstract

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 ϩ/ϩ bowel but absent in the SERT Ϫ/Ϫ bowel. However, both the SERT ϩ/ϩ gut and the Ϫ/Ϫ 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 Ϫ/Ϫ bowel, which contained mRNA encoding tryptophan hydroxylase, but no 5-HT was present in the blood of SERT Ϫ/Ϫ animals. Stool water and colon motility were increased in most SERT Ϫ/Ϫ 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 Ϫ/Ϫ mice, whereas the transient constipation may be caused by episodes of enhanced 5-HT release leading to 5-HT receptor desensitization.

Serotonin Uptake Is Largely Mediated by Platelets versus Lymphocytes in Peripheral Blood Cells

“…33,34 The gene that is responsible for SERT expression in the brain has been shown to code for SERT in peripheral blood cells. [35][36][37]20 Platelets are small 2−3 μM anucleate cell fragments derived from megakaryocytes that are primarily responsible for hemostasis and blood clotting. 38 Platelets have long been known to express SERT, 38,32 and more recently dopamine transporter (DAT) expression has been identified in platelets.…”

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

“…Recent reports have confirmed the relevance of the SERT function for the control of intestinal activity [30,31]. SERT expression and activity are affected in intestinal inflammation [10,[14][15][16] and inflammatory mediators have been shown to inhibit SERT function and expression in epithelial cells [12,13].…”

O Eixo Intestino-Cérebro E O Papel Da Serotonina

“…As células enteroendócrinas produzem e secretam muito mais serotonina em comparação aos neurônios serotoninérgicos centrais ou periféricos, de forma que a serotonina secretada pelas células enteroendócrinas podem ser liberadas para o lúmen gastrointestinal (GRONSTARD et al, 1985;WINGREN et al, 1988) e o sangue (MORRIS-SEY; WALKER; LOVENBERG, 1977;TAMIR et al, 1985;CHEN et al, 2001).…”

“…Dessa forma, após a 5-HT ser sintetizada pelas cé-lulas enteroendócrinas da mucosa intestinal (GERSHON, 2004) parte, é usada localmente como um neurotransmissor do SNE (GERSHON;TACK, 2007;CHEN et al, 2001) enquanto outra parte da 5-HT se difunde do intestino para a circulação sanguínea, onde a maior parte é rapidamente eliminada pelo fígado e pulmões (THOMAS; VANE, 1967;ANDERSON;STEVENSON;COHEN, 1987), restando apenas a serotonina que é captada pelas plaquetas, única fonte de serotonina sérica (ERSPAMER, 1966;MORRISSEY;WALKER;LOVENBERG, 1977).…”