Ontogeny regulates creatine metabolism in rat small and large intestine

Area of Science:

• Physiology
• Developmental Biology
• Molecular Biology

Background:

• Creatine is vital for cellular energy homeostasis.
• Intestinal creatine transport and synthesis pathways are not fully understood.
• Understanding the ontogeny of these pathways is crucial for metabolic research.

Purpose of the Study:

• To investigate the developmental changes in intestinal creatine transporter (CRT), arginine:glycine amidinotransferase (AGAT), and guanidinoacetate N-methyltransferase (GAMT) in rats.
• To characterize the properties and localization of intestinal CRT.
• To elucidate the regulatory mechanisms of creatine synthesis during maturation.

Main Methods:

• Investigated ontogeny in rat tissues (foetal to adult).
• Assessed CRT activity, Na(+)/Cl(-) dependence, and inhibition kinetics.
• Utilized Northern assays, in situ hybridization, immunohistochemistry, and Western assays.
• Quantified AGAT and GAMT mRNA levels in intestinal and renal tissues.

Main Results:

• Colon CRT is Na(+)- and Cl(-)-dependent, localized to the apical membrane of epithelial cells, with two mRNA transcripts.
• Colonic CRT activity decreases with maturation, while CRT mRNA abundance increases.
• Specific CRT protein isoforms (57, 65, 80, 116 kDa) show age-dependent changes.
• Intestinal AGAT mRNA abundance decreases with maturation, while GAMT mRNA remains stable.
• Renal AGAT mRNA levels increase with age.

Conclusions:

• The apical membrane of the rat colon possesses an active creatine transporter (CRT).
• Development down-regulates colonic CRT activity through post-transcriptional mechanisms.
• The intestine may synthesize creatine, with its synthesis regulated by AGAT gene expression during development.
• Intestinal and renal creatine synthesis are developmentally regulated at the AGAT gene expression level.