Metabolism of prostaglandins A and E in the perfused rabbit lung and the effects of selected inhibitors.
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).
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
D011454:Prostaglandins A; D011458:Prostaglandins E; D014662:Vasoconstrictor Agents; D010643:Phenoxybenzamine; D010042:Ouabain; D010693:Phloretin