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

Abstract

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.