METABOLISM OF PROSTAGLANDINS-A1 AND E1 IN PERFUSED RABBIT LUNG AND EFFECTS OF SELECTED INHIBITORS

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 198  (3) , 716-724
Abstract
Hypothermia (4.degree. 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 .mu.M) and PGE1 (2.8 .mu.M) resulted in 48% inhibition of PGA1 metabolism. Ouabain and phenoxybenzamine (10-5 M) did not signficantly affect PGA1 metabolism. The effect of diphloretin phosphate (DPP; 6.0 .mu.g/ml) was studied on the metabolism of prostaglandin A1 (0.28-5.03 .mu.M) and E1 (PGE1; 0.28-11.56 .mu.M). 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 (.mu.M) and apparent Vmax (nmol/lung .times. 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. DPP acts in a noncompetitive manner. The magnitude of inhibition of PGA1 and PGE1 metabolism (both at 0.28 .mu.M) was linearly related to the DPP concentration, over the range of 0.06-25.0 .mu.g/ml. The ID50 [median inhibitory does] values of DPP inhibition of PGA1 and PGE1 metabolism were 2.2 and 8.4 .mu.g/ml, respectively. Perfusion of PGA1 at 2.96 .mu.M or higher concentrations caused reversible vasoconstriction which was significantly inhibited (P < .05) by DPP (6.0 .mu.g/ml) by an average of 77.2 .+-. 5.8% (n = 7).

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