Desensitization to locally injected PGF_2α as reflected in the vascular permeability and collagen and noncollagenous protein synthesis of carrageenin-induced granulation tissue in rats

Administration of PGF_2α at doses of 50 and 250 μg into pouch fluid (calculated concentration of PGF_2α was about 4 and 14 μg/ml of pouch fluid, respectively) of 7-day-old carrageenin granuloma in rats depressed vascular permeability, as measured by leakage of radioiodinated human serum albumin into the pouch fluid. However, 3 hr after PGF_2α treatment at a dose of 50 μg. the vascular permeability had recovered to control level; 3 hr after a dose of 250 μg PGF_2α, the vascular permeability had not recovered completely. The uptake of [³H]proline into collagen hydroxyproline and noncollagenous protein of carrageenin granuloma tissue was also examined. It was found that the first injection of PGF2a at a dose of 50 or 250 μg depressed the uptake of [³H]proline into both protein fractions, but 3 hr after the first injection of PGF_2α, there was no significant difference in uptake between the control and the PGF_2α-treated group. A study of the metabolism of PGF_2α in a homogenate of granulation tissue and in pouch fluid showed little activity in the former and very little activity in the latter. In the homogenate, about 70 per cent of the originally added [³H]PGF_2α remained unmetabolized after 3 hr of incubation. In the inflammatory fluid, less than 20 per cent of the radioactivity present at 35 min after the injection had dissappeared from the pouch fluid at 3 hr after the [³H]PGF_2α injection; all the remaining radioactivity was found to be unmetabolized [³H]PGF_2α. Consequently, it was suggested that the tissue became desensitized to the injected PGF_2α. To confirm this suggestion, another 50 or 250 μg of PGF_2α was injected 3 hr after the first PGF_2α injection. However, a decrease in vascular permeability and in uptake of [³H]proline into both protein fractions after the second injection of PGF_2α were not observed. It was concluded that, 3 hr after the first PGF_2α treatment, the sensitivity of the carrageenin-induced granulation tissue to PGF_2α had decreased.