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Diurnal rhythm of H+-peptide cotransporter in rat small intestine
Xiaoyue Pan1, Tomohiro Terada, Megumi Irie
1Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606 - 8507, Japan.
Insights
The intestinal H+-peptide cotransporter (PEPT1) shows daily rhythm in activity and expression, peaking at night. This diurnal regulation may influence dietary protein absorption in mammals.
Area of Science:
- Chronobiology
- Mammalian physiology
- Molecular biology
Background:
- Circadian rhythms regulate numerous physiological processes in mammals.
- The H+-peptide cotransporter 1 (PEPT1) is crucial for absorbing peptides and peptide-like drugs in the small intestine and kidney.
Purpose of the Study:
- To investigate the diurnal rhythm of intestinal and renal PEPT1 expression and function.
- To compare PEPT1 diurnal variations with those of the Na+-glucose cotransporter 1 (SGLT1).
Main Methods:
- Studied diurnal rhythm in rats under a 12-h light-dark cycle.
- Assessed [14C]glycylsarcosine (Gly-Sar) transport using in situ intestinal loops and everted intestinal preparations.
- Quantified PEPT1 and SGLT1 protein and mRNA levels at different time points.
Main Results:
- Intestinal PEPT1 transport activity and expression (protein and mRNA) exhibited significant diurnal variations, with higher levels during the dark phase.
- Similar diurnal patterns were observed for intestinal Na+-glucose cotransporter 1 (SGLT1).
- Renal PEPT1 and SGLT1 showed minimal diurnal rhythmicity in expression.
Conclusions:
- Intestinal PEPT1 activity and expression are under diurnal regulation.
- This regulation could impact the absorption of dietary peptides and peptide-like drugs.
- Diurnal rhythmicity is more pronounced in intestinal transporters compared to renal ones.
Abstract:
In mammals, most physiological, biochemical, and behavioral processes show a circadian rhythm. In the present study, we examined the diurnal rhythm of the H+-peptide cotransporter (PEPT1), which transports small peptides and peptide-like drugs in the small intestine and kidney, using rats maintained in a 12-h photoperiod with free access to chow. The transport of [14C]glycylsarcosine (Gly-Sar), a typical substrate for PEPT1 by in situ intestinal loop and everted intestine, was greater in the dark phase than the light phase. PEPT1 protein and mRNA levels varied significantly, with a maximum at 2000 and minimum at 800. Similar functional and expressional diurnal variations were observed in the intestinal Na+-glucose cotransporter (SGLT1). In contrast, renal PEPT1 and SGLT1 showed little diurnal rhythmicity in protein and mRNA expression. These findings indicate that the intestinal PEPT1 undergoes diurnal regulation in its activity and expression, and this could affect the intestinal absorption of dietary protein.