Prostanoid biosynthesis in patients with cystic fibrosis.
The urinary excretion rate (ng/h/1.73 m2) of prostanoids was determined with a capillary gas-liquid chromatographic mass spectrometric method in 19 patients with cystic fibrosis (CF) aged 1-29 years. Patients with CF showed an increased excretion of prostaglandin E2 metabolites (PGE-M) and thromboxane B2 and its metabolites at all ages. An imbalance in the excretion pattern of thromboxane B2 metabolites also suggested a relative impairment of beta-oxidation. There was no increased excretion of dinor-6-keto-PGF1 alpha, indicating normal prostacyclin biosynthesis. No correlation was found to genotype, clinical score, lung function or bacterial colonization but a significant negative relation was found between the main prostanoids in the urine and serum phospholipid levels of essential fatty acids. The results show that, contrary to the generally accepted decrease of prostanoid excretion in essential fatty acid deficiency, patients with CF increase their production parallel to the development of the deficiency. Since prostanoid synthesis is rate limited by arachidonic acid release, our data support a previously presented hypothesis about a pathological regulation of the release of arachidonic acid in CF.
Strandvik
B
B
Department of Pediatrics, Faculty of Medicine, Göteborg University, Sweden.
Svensson
E
E
Seyberth
H W
HW
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism / Q000652:urine; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism / Q000652:urine; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000097:blood; D008297:Male; D010743:Phospholipids / Q000097:blood / Q000737:chemistry; D011453:Prostaglandins / Q000096:biosynthesis* / Q000652:urine*; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000378:metabolism; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine
D005227:Fatty Acids; D008041:Linoleic Acids; D010743:Phospholipids; D011453:Prostaglandins; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D019787:Linoleic Acid; D011464:Epoprostenol; D015232:Dinoprostone