Ascorbic acid promotes prostanoid release in human lung parenchyma.
Ascorbic acid reduces airway reactivity to inhaled bronchoconstrictor agents in man and guinea pigs. The precise mechanism(s) responsible for this effect are unknown, but in both species an acute indomethacin treatment reverses the action of the ascorbic acid. To determine if ascorbic acid promotes prostanoid synthesis and/or inhibits degradation, human lung parenchymal slices (100-200 mg) were incubated for 60 minutes in oxygenated Tyrode's solution alone or with sodium ascorbate (0.001 M-1 M) and/or methacholine (1 microM-100 microM) and/or indomethacin (0.17 microM-17 microM). Aliquots of the incubation medium were assayed by radioimmunoassay for PGE2, PGF2 alpha, thromboxane B2 and 6-keto-PGF1 alpha. Ascorbic acid increased the accumulation of all four prostanoids in the incubation medium, especially thromboxane B2 and 6-keto-PGF1 alpha. This stimulatory effect of ascorbic acid was concentration-dependent and was inhibited by indomethacin. We conclude that ascorbic acid can alter prostanoid generation by human lung tissue and this effect may, in part, explain its antibronchoconstrictor activity in man.
D001205:Ascorbic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008175:Lung Neoplasms / Q000601:surgery; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D012907:Smoking
D008688:Methacholine Compounds; D011453:Prostaglandins; D016210:Methacholine Chloride; D001205:Ascorbic Acid