Functional expression of carnitine/organic cation transporter OCTN1/SLC22A4 in mouse small intestine and liver

Area of Science:

• Pharmacology
• Molecular Biology
• Physiology

Background:

• The carnitine/organic cation transporter 1 (OCTN1/SLC22A4) is known to transport various drugs.
• Its precise physiological function in organs like the small intestine and liver remains largely uncharacterized.
• Understanding OCTN1's role is crucial for drug delivery and nutrient absorption studies.

Purpose of the Study:

• To investigate the functional expression and role of OCTN1 in the small intestine and liver.
• To elucidate the contribution of OCTN1 to the absorption and distribution of its substrate, ergothioneine (ERGO).

Main Methods:

• Utilized octn1 gene knockout (octn1(-/-)) mice and wild-type littermates.
• Administered radiolabeled [(3)H]ergothioneine ([(3)H]ERGO) orally and intravenously.
• Performed in vitro uptake studies using cell lines and isolated intestinal/hepatic cells.
• Conducted immunohistochemical analysis for OCTN1 localization.

Main Results:

• octn1(-/-) mice showed significantly higher amounts of [(3)H]ERGO remaining in the small intestinal lumen post-oral administration.
• Uptake of [(3)H]ERGO in intestinal tissues and OCTN1-expressing cells was inhibited by known OCTN1 substrates.
• Immunohistochemistry confirmed OCTN1 localization on the apical surface of the small intestine in both mice and humans.
• Plasma concentrations of [(3)H]ERGO were higher in octn1(-/-) mice, suggesting efficient hepatic uptake.
• OCTN1 was found to be functionally expressed in non-parenchymal liver cells, not hepatocytes.

Conclusions:

• OCTN1 plays a significant role in the intestinal absorption of ergothioneine.
• OCTN1 is functionally expressed in the non-parenchymal cells of the liver, contributing to hepatic uptake.
• These findings highlight OCTN1's importance in both intestinal absorption and hepatic disposition of ergothioneine.