TY - JOUR T1 - Metabolism of prostaglandins A and E in the perfused rabbit lung and the effects of selected inhibitors. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 716 LP - 724 VL - 198 IS - 3 AU - K B Gross AU - C N Gillis Y1 - 1976/09/01 UR - http://jpet.aspetjournals.org/content/198/3/716.abstract N2 - 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). ER -