Dependence of pulmonary prostaglandin metabolism on carrier-mediated transport processes.
Inhibitors of prostaglandin (PG) transport (probenecid, indomethacin, or bromcresol green) were found to eliminate the difference between the pulmonary transit time of 3H and 14C when [3H]PGF2alpha and E114C]sucrose were injected as a single intra-arterial bolus into the isolated perfused rat lung. Similar results were obtained with PGE1. The transit time of [3H]PGA1 was not significantly different from that of [14C]sucrose even in the absence of an inhibitor. These inhibitors increased the amount of [3H]PGF2alpha or [3H]PGE1 and decreased the amount of [3H]PG metabolites found in the venous effluent: these agents also inhibited the pulmonary metabolism of continously infused, nonradioactive PGF2alpha. One of the three inhibitors, bromcresol green, was shown not to be an effective inhibitor of PG metabolism in cell-free preparations of rat lung homogenates. These results indicated that under normal conditions, PG's are rapidly transported into intracellular compartment(s) where they are metabolized. Inhibition of this transport process prevents rapid access of PG's to the cytoplasmic enzymes and therefore inhibits pulmonary PG metabolism. This implies that inhibitors of PG transport, including anti-inflammatory organic acids, and some PG antagonists, metabolites, and analogues, can be expected to inhibit the pulmonary metabolism of PG's and thus could potentiate the systemic effects endogenous or exogenous PG's.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001961:Bromcresol Green / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007458:Iodipamide / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D013395:Sucrose / Q000378:metabolism*
D011453:Prostaglandins; D013395:Sucrose; D001961:Bromcresol Green; D011339:Probenecid; D007458:Iodipamide; D007213:Indomethacin