Selective inhibition of rat lung cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase by cyclic nucleotides and their analogues and various drugs [proceedings].

the effect of serum proteins or indomethacin on prostaglandin synthase is assayed important in determining the potency of inhibitors, but also the fact that studies of inhibition of a complex multienzyme system such as ‘prostaglandin synthase’, even under optimal conditions, are complicated by the fact that haptoglobin and albumin can interact with different components of the enzyme ststem (Denning-Kendall et ul., 1980). It is evident from the above data that, at lower enzyme concentration, the inhibition of prostaglandin synthase by serum proteins is proportionally higher, whereas indomethacin gave maximal inhibition at higher enzyme concentrations. It should be noted that these effects of varying enzyme concentration were obtained at substrate concentrations closely approximating those thought to exist in vivo (Ho & Esterman, 1974). However, as seen with albumin and indomethacin (Table l), the substrate concentration of the enzyme reaction is also important, in determining their inhibitory potency. This finding is in general agreement with the observations of others (Flower, 1974; Ho & Esterman, 1974). The above considerations may affect the actions of haptoglobin and albumin in vivo. Haptoglobin is likely to be more active in certain tissues that have low prostaglandin synthase activities (Christ & Van Dorp, 1972), but unlike indomethacin or albumin, its inhibitory potency will remain unaffected by changes in the substrate concentration.