Pulmonary O-methyl transferases.

An investigation 111 vitro of pulmonary O-methyl transferases rcvcaled the presence of microsomal phenol-O-methyl transferase and soluble and microsomal catechol-O-methyl transferases in guineapig lung tissue. Both phenol and catechol transferases also were detected in rat and rabbit lung tissue. Substrates of guinea-pig pulmonary phenol-0-mcth!l transfcrasc ~ncludcJ phenols. crcsols and xylenols. but not alcohols and amines. Catcchol-0-methyl transferaaes from both subcellular sources were found to have similar pH optima. magnesium ion requirements, K,,, values, and utilircd norepinephrine. isoprotcrcnol and dopamine as suhstratcs, but not metaprotcrcnol and salbutamol. These data for the pulmonary enzymes are similar to published values for liver 0-methyl transfcrascs. It is recognized that the lung may have at least a secondary role similar to that of the liver in the detoxification or activation of exogenous compounds [I]. In support of this hypothesis are the common embryonic origin of lung and liver [?I, and the efficient inactivation of many endogenous substances in a single passage through the lungs 131. It is also significant in this regard that foreign compounds entering the body other than through the gastrointestinal tract would pass through the lungs before reaching the arterial circulation and the liver. Nevertheless, relatively little has been reported concerning the biotransformations of exogenous materials by lung tissue. The presence of benzpyrene hydroxylase has been established in rat lungs [46] and more recently the mixed-function oxidases of liver and lung tissue have been compared [7-I I]. The soluble fraction of rabbit lung homogenate in the presence of Sadenosyl-[/nrth_r/-‘4C]methionine promotes the Nmethylation of a diverse series of amines [12, 131. Hovvevcr. studies of O-methyl transferases in lungs have been limited as part of more general studies of tissue and species distribution of the enzymes involved. For example, phenol-O-methyl transferase has been reported 1141 to be present in guinea-pig with the lung tissue portion of the study being limited to phenol per se. In a similar study, catechol-O-methyl transferasc has been detected in rat lung homogenates [ 151. It is the purpose of this paper to further characterize O-methyl transferases in subcellular fractions prepared from guinea-pig lungs. * Supported in part by Institutional Research Grant IN 4OL from the American Cancer Society and a grant from the University of Michigan Cancer Research Institute. Abstracted from a dissertation submitted in partial fulfillment of the requirements for the Doctor of Philosophy degree. Present address: National Institute of Environmental Health Sciences. Research Trldngle Park, N. C. 27709. M.~TEKIALS AND METHODS