Influence of genetic knockout of Pept2 on the in vivo disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice
Laboratory studyOther animals
- Design
- Laboratory study
- Subjects
- Gender- and weight-matched Pept2+/+ and Pept2-/- mice, 8 to 10 weeks old, C57BL/6 background; n = 10 for plasma pharmacokinetics, n = 7 for tissue distribution and renal clearance, n = 4 to 7 for endogenous tissue levels, n = 4 for metabolic stability
- Dose used in the study
- Single intravenous tail-vein bolus of tritiated carnosine, 1 nmol per g body weight
- Duration
- Serial blood sampling over 30 minutes with terminal collection of blood, CSF, urine and tissues at 30 minutes
- What was measured
- Plasma pharmacokinetics (clearance, AUC), renal clearance and fractional reabsorption, CSF-to-plasma ratio and tissue distribution of exogenous tritiated carnosine; endogenous carnosine in plasma, CSF, choroid plexus, cerebral cortex, olfactory bulb, kidney, spleen and skeletal muscle by HPLC with fluorescence detection.
What the authors reported
In Pept2 null mice systemic clearance of carnosine was higher (0.50 versus 0.29 ml/min) and exposure lower (AUC 43.7 versus 73.0 min x microM) than in wild-type. Renal clearance was about 18-fold higher in null mice (206 versus 11.5 microlitres/min) and fractional reabsorption fell from 0.94 to 0.20. The CSF-to-plasma ratio was about eightfold higher in null mice (0.70 versus 0.08). Endogenous carnosine was lower in choroid plexus, olfactory bulb and spleen and higher in skeletal muscle of null mice, with no difference in plasma or CSF.
Limits of this study
Mouse study with intravenous dosing, so it does not describe oral absorption. Short 30-minute observation window. The abstract gives an 18-fold renal clearance difference while the results text gives about 17-fold. This is the PEPT2 renal carnosine uptake paper described in the brief; its PMID is 19225147, not 18820998.
Source
PubMed 19225147 · doi:10.1152/ajpregu.90744.2008
Entry checked against Full text PDF via academia.edu/51260501 (abstract, methods, group sizes); reference entry in Pharm Res 2023, doi 10.1007/s11095-023-03550-9; PMID from Google Scholar lookup link returned by search (scholar.google.com/scholar_lookup?doi=10.1152/ajpregu.90744.2008&pmid=19225147). Journal page and PMC2698603 blocked at time of checking. on 2026-10-17. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.