Fig. 1.

l-4F that is introduced directly into the circulation preferentially associates with the proximal small bowel. A: Gross tissue distribution was first determined by injecting ¹⁴C-4F (25 mg/kg, 0.2 μCi) into C57BL/6J mice via the tail vein (n = 3). After 60 min, the mice were euthanized and perfused, tissues were dissected and homogenized, and radioactivity was determined by scintillation counting. Counts were significantly higher in the SI compared with the liver (* P = 0.04). B: ¹⁴C-l-4F (25 mg/kg, 2 μCi) was injected via tail vein directly into the circulation of each of 15 fasted C57BL/6J mice. At various time points, the animals were euthanized, perfused, and dissected, and radioactivity was determined (3 mice/time point). A significant increase in radioactivity between 3 and 60 min was observed for both the duodenum (* P = 0.003) and the jejunum (** P = 0.001). C, D: l-4F or d-4F (25 mg/kg) was injected via tail vein into C57BL/6J mice (n = 4 per peptide). After 15 min, the animals were euthanized and perfused, and levels of intact peptide were determined in intestinal tissue via LC/MS/MS. Both peptides exhibited distribution patterns comparable to each other and to that at 15 min and 60 min in B. The concentrations of intact l-4F and d-4F were both significantly higher in the duodenum compared with the jejunum (* P = 0.001 and P = 0.005, respectively). Error is reported as SEM.