16-16-dimethylprostaglandin-e2 and enisoprost

The interactions of bradykinin (BK) and FMLP (a leukocyte-dependent mediator of inflammation) with thirteen prostaglandin E analogs have been investigated in a rabbit skin model of inflammation. The PGE analogs were chosen with a view to defining the EP-receptor subtypes involved. Five analogs, PGE2, misoprostol, 16,16-dimethyl PGE2, nocloprost, and enisoprost, were potent vasodilators (133Xe clearance method) and potent potentiators of both BK and FMLP exudation ([125I]albumin method). A further four analogs, butaprost, 11-deoxy PGE1, mexiprostil, and AH 13205, were weaker vasodilators and weaker potentiators of exudation. The remaining four analogs, 11-deoxy PGE2-1-alcohol, MB 28767, sulprostone, and GR 63779X did not induce vasodilatation and did not potentiate FMLP exudation. However, the latter three prostanoids (which are all potent and moderately selective EP3 agonists) produced a modest potentiation of BK exudation at low doses (1 and 10 ng), with no greater effect at higher doses (100 and 1000 ng). Statistical correlation of vasodilator responses with potentiation of FMLP exudation responses was highly significant. A similar correlation for vasodilation/BK exudation, although statistically significant, was not as convincing. The analyses suggested that vasodilatation is a major mechanism of PGE-induced potentiation of plasma exudation and that an EP2-receptor subtype is involved. However, the possibility of a second non-dilator mechanism could not be ruled out.

Topics: 16,16-Dimethylprostaglandin E2; Alprostadil; Animals; Biphenyl Compounds; Blood Flow Velocity; Bradykinin; Dermatitis; Dinoprostone; Drug Synergism; Flurbiprofen; Heptanoic Acids; Kinetics; Male; Misoprostol; N-Formylmethionine Leucyl-Phenylalanine; Prostaglandins F, Synthetic; Rabbits; Receptors, Prostaglandin E; Skin; Vasodilation

Bacterial translocation and related mortality rates were examined in previously transfused BALB/c mice that were gavaged with 14C radioisotope-labeled Escherichia coli before inflicting a 20% full-thickness flame burn. Radionuclide counts were measured in blood obtained by retro-orbital puncture 4 hours postburn, and survival was recorded for 10 days. Radionuclide counts in the blood correlated well with both radionuclide counts and numbers of viable bacterial in the tissues. Survivors had significantly less bacterial translocation as evidenced by blood radionuclide counts compared with nonsurvivors, and there was a significant inverse correlation between the degree of translocation and the length of survival. In the next experiment, the prostaglandin E (PGE) analogs misoprostol, enisoprost, or 16,16-dimethyl PGE2 were administered to transfused animals for 3 days before burn. Prostaglandin E analogs significantly reduced bacterial translocation as measured by blood radionuclide counts 4 hours postburn and improved survival. The data demonstrate that the intensity of bacterial translocation after burn injury is significantly associated with subsequent death. Improvement of survival by PGE analogs is associated with decreased bacterial translocation.

Topics: 16,16-Dimethylprostaglandin E2; Alprostadil; Animals; Burns; Colony Count, Microbial; Escherichia coli; Female; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Misoprostol; Prostaglandins E, Synthetic