Effects of Capsaicin on Intestinal Cephalexin Absorption in Rats

Komori, Yukiko; Aiba, Tetsuya; Sugiyama, Risa; Nakai, Chie; Kawasaki, Hiromu; Kurosaki, Yuji

doi:10.1248/bpb.30.547

Cited by 12 publications

(12 citation statements)

References 33 publications

(41 reference statements)

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“…The role of vagal afferents in the regulation of intestinal transporter expression is even less well studied. Studies have shown that intraluminal capsaicin infusion (which is acutely excitatory on vagal afferents) in the short term suppresses alanine transport and expression of the PepT1 peptide transporter (2,18). In contrast, vagal deafferentation leads to upregulation of alanine transport (25).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1

Stearns¹,

Balakrishnan²,

Rounds³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Stearns AT, Balakrishnan A, Rounds J, Rhoads DB, Ashley SW, Tavakkolizadeh A. Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na ϩ /glucose cotransporter SGLT1. Am J Physiol Gastrointest Liver Physiol 294: G1078-G1083, 2008. First published February 28, 2008 doi:10.1152/ajpgi.00591.2007.-Introduction: the intestinal Na ϩ /glucose cotransporter (SGLT1) displays rapid anticipatory diurnal rhythms in mRNA and protein expression. The vagus nerve has been implicated in the entrainment of some transporters. We aimed to clarify the influence of the vagus nerve on the diurnal entrainment pathway for SGLT1 and examine the role of vagal afferent fibers. Methods: male Sprague-Dawley rats were randomized to three groups, total subdiaphragmatic vagotomy, selective deafferentation of the vagus with capsaicin, or sham laparotomy. Postoperatively, animals were maintained in a 12-h light-dark cycle with food access limited to night. On the ninth postoperative day, animals were euthanized to harvest jejunal mucosa at 6-h intervals starting at 10 AM. Whole cell SGLT1 protein was measured by semiquantitative densitometry of immunoblots. Sglt1 and regulatory subunit RS1 mRNA was assessed by quantitative PCR. Fluorogold tracer technique was used to confirm adequacy of the vagotomy. Results: the diurnal rhythm in intestinal SGLT1, with a 5.3-fold increase in Sglt1 mRNA at 4 PM, was preserved in both vagotomy and capsaicin groups. However, the rhythmicity in SGLT1 protein expression (2.3-fold peak at 10 PM; P ϭ 0.041) was abolished following either total vagotomy or deafferentation. Lack of change in RS1 mRNA suggests this is independent of the RS1 regulatory pathway. Conclusion: SGLT1 transcription is independent of the vagus. However, dissociation of the protein rhythm from the underlying mRNA signal by vagotomy suggests the vagus may be involved in posttranscriptional regulation of SGLT1 in an RS1 independent pathway. Disruption following afferent ablation by capsaicin suggests this limb is specifically necessary. glucose transport; vagus; vagotomy THE APICAL na ϩ /glucose cotransporter (SGLT1), localized on the brush-border membrane of small bowel enterocytes, is responsible for all secondary active absorption of glucose from the small bowel (14,19). Dysregulation of SGLT1 is increasingly recognized in type 2 diabetes mellitus, with expression increasing up to fourfold in both patients and animal models (4, 7-9). Similarly, knockout of the SGLT1 regulatory subunit protein RS1 in mice leads to both SGLT1 overexpression and severe obesity (27). Therapy aimed at modulating SGLT1 expression may therefore have clinical benefits in diabetes and obesity through slowing of glucose absorption in a manner similar to amylase inhibitors (5) and through increased ileal glucose delivery (38). SGLT1 expression is regulated by several inputs, including diet composition (11) and the timing of food intake (28). Despite significant progress in characterizing the physiological signaling mechanisms regulating SGL...

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Section: Discussionmentioning

confidence: 99%

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1

Stearns¹,

Balakrishnan²,

Rounds³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Paracellular uptake of peptides or peptidomimetics may also be influenced by bioactive components in the diet. Capsaicin, the chemical responsible for the pungent properties of hot peppers, was shown to reduce uptake of cephalexin in the jejunum and ileum of rats, primarily due to a decrease in transcellular transport mediated by PepT1 (Komori et al, 2007). Interestingly, capsaicin increased the paracellular permeabililty of cephalexin.…”

Section: Alternative Mechanisms Of Peptide Uptakementioning

confidence: 99%

BOARD-INVITED REVIEW: Peptide absorption and utilization: Implications for animal nutrition and health

Gilbert

Wong

Webb

2008

Journal of Animal Science

290

209

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Over the last 50 yr, the study of intestinal peptide transport has rapidly evolved into a field with exciting nutritional and biomedical applications. In this review, we describe from a historical and current perspective intestinal peptide transport, the importance of peptides to whole-body nutrition, and the cloning and characterization of the intestinal peptide transporter, PepT1. We focus on the nutritional significance of peptide transport and relate these findings to livestock and poultry. Amino acids are transported into the enterocyte as free AA by a variety of AA transporters that vary in substrate specificity or as di- and tripeptides by the peptide transporter, PepT1. Expression of PepT1 is largely restricted to the small intestine in most species; however, in ruminants, peptide transport and activity is observed in the rumen and omasum. The extent to which peptides are absorbed and utilized is still unclear. In ruminants, peptides make a contribution to the portal-drained visceral flux of total AA and are detected in circulating plasma. Peptides can be utilized by the mammary gland for milk protein synthesis and by a variety of other tissues. We discuss the factors known to regulate expression of PepT1 including development, diet, hormones, diurnal rhythm, and disease. Expression of PepT1 is detected during embryological stages in both birds and mammals and increases with age, a strategic event that allows for the immediate uptake of nutrients after hatch or birth. Both increasing levels of protein in the diet and dietary protein deficiencies are found to upregulate the peptide transporter. We also include in this review a discussion of the use of dietary peptides and potential alternate routes of nutrient delivery to the cell. Our goal is to impart to the reader the nutritional implications of peptide transport and dietary peptides and share discoveries that shed light on various biological processes, including rapid establishment of intestinal function in early neonates and maintenance of intestinal function during fasting, starvation, and disease states.

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“…Selected ingredients are also able to influence metabolic pathways of Pept1. The alkaloid capsaicin, found in chili peppers, was shown to block cephalexin absorption from jejunum which may be explained by alterations in PEPT1 activity and changes in intracellular calcium [84]. This effect was also observed in Caco-2 cells, which were treated with a Ca 2+ blocker [85] and it seems that a reduced cellular Ca 2+ concentration stimulates NHE3 activity and thereby increases PEPT1-functions [25].…”

Section: Other Dietary Factors Regulating Pept1mentioning

confidence: 99%

Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1

Näßl

Rubio‐Aliaga

Fenselau

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Neither gene expression nor proteome profiling nor functional analysis revealed evidence for any compensatory changes in the levels and/or function of transporters for free amino acids in the intestine. However, most plasma amino acid levels were increased in Pept1(-/-) compared with Pept1(+/+) animals, suggesting that amino acid handling is altered. Plasma appearance rates of (15)N-labeled amino acids determined after intragastric administration of a low dose of protein remained unchanged, whereas administration of a large protein load via gavage revealed marked differences in plasma appearance of selected amino acids. PEPT1 seems, therefore, important for overall amino acid absorption only after high dietary protein intake when amino acid transport processes are saturated and PEPT1 can provide additional absorption capacity. Since renal amino acid excretion remained unchanged, elevated basal concentrations of plasma amino acids in PEPT1-deficient animals seem to arise mainly from alterations in hepatic amino acid metabolism.

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Effects of Capsaicin on Intestinal Cephalexin Absorption in Rats

Cited by 12 publications

References 33 publications

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1

BOARD-INVITED REVIEW: Peptide absorption and utilization: Implications for animal nutrition and health

Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1

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Effects of Capsaicin on Intestinal Cephalexin Absorption in Rats

Cited by 12 publications

References 33 publications

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na+/glucose cotransporter SGLT1

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na+/glucose cotransporter SGLT1

BOARD-INVITED REVIEW: Peptide absorption and utilization: Implications for animal nutrition and health

Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1

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Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1