title: Metabolism of prostaglandins A and E in the perfused rabbit lung and the effects of selected inhibitors.
abstract: Hypothermia (4 degrees C) reversibly inhibits metabolism of prostaglandin A1 (PGA1) in the perfused rabbit lung and decreases the transit time of PGA1 through the lung. Co-perfusion of PGA1 (0.28 muM) and PGE1 (2.8 muM) resulted in 48% inhibition of PGA1 metabolism. Ouabain and phenoxybenzamine (10(-5) M) did not significantly affect PGA1 metabolism. We examined the effect of diphloretin phosphate (DPP; 6.0 mu/ml) on the metabolism of prostaglandin A1 (0.28-5.03 muM) and E1 (PGE1;0.28-11.56 muM). The metabolism of both prostaglandins appeared to be saturable processes and, in the case of PGE, the data conformed to Michaelis-Menten kinetics: the apparent Km (muM) and apparent Vmax (nmol/lung X min-1) in control lungs were 9.0 +/- 0.3 and 87.9 +/- 1.4, respectively, and in the DPP-treated lungs were 9.6 +/- 0.5 and 57.7 +/- 1.8. This suggests that DPP acts in a noncompetitive manner. The magnitude of inhibition of PGA1 and PGE1 metabolism (both at 0.28 muM) was linearly related to the DPP concentration, over the range of 0.06 to 25.0 mug/ml. The ID50 values of DPP inhibition of PGA1 and PGE1 metabolism were 2.2 and 8.4 mug/ml, respectively. Perfusion of PGA1 at 2.96 muM or higher concentrations caused reversible vasoconstriction which was significantly inhibited (P less than .05) by DPP (6.0 mug/ml) by an average of 77.2 +/- 5.8% (n = 7).
mesh_terms: D000818:Animals; D003080:Cold Temperature; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D010643:Phenoxybenzamine / Q000494:pharmacology; D010693:Phloretin / Q000031:analogs & derivatives / Q000494:pharmacology; D011454:Prostaglandins A / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D014662:Vasoconstrictor Agents
chemical_list: D011454:Prostaglandins A; D011458:Prostaglandins E; D014662:Vasoconstrictor Agents; D010643:Phenoxybenzamine; D010042:Ouabain; D010693:Phloretin