nocloprost and Dermatitis

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

Vasodilatory prostaglandins (PG), contributing to the inflammatory reaction, have gained considerable attention. It is becoming apparent that PG have pharmacological effects traceable to biological activities distinct from smooth muscle relaxation. The data from pharmacological experiments presented here indicate the diverse action of vasodilatory PG analogues in the skin of laboratory animals. Nocloprost, a stable PGE2 analogue, induced erythema in intact skin of rats when applied topically and inhibited in the same dose range an irritant-induced inflammatory reaction in the ears of mice. Iloprost, a stable PGI2 analogue, showed proinflammatory activity after local application by enhancing the leukotriene B4 induced cell infiltration in the skin of mice. The attenuation of the spreading of ear necrosis in mice, on the other hand, indicates an anti-ischemic therapeutic potential of iloprost. Research in the past has elucidated the influence of PG on the vascular component of inflammation, but the role of PG on the cellular component of inflammation is less clear. The diverse effects of PG in skin indicate the need for a better understanding of their local actions.

Topics: Animals; Dermatitis; Female; Iloprost; Leukotriene B4; Male; Mice; Prostaglandins; Prostaglandins F, Synthetic; Rats; Rats, Wistar; Skin