Metabolism and cardiovascular effects of leukotrienes in the marine toad Bufo marinus.

Leukotriene (LT) metabolism and physiology have been studied extensively in mammals; however, little is known of their roles in nonmammalian vertebrates. This study examines the cardiovascular effects of leukotrienes on blood pressure and heart rate in the conscious and cannulated marine toad, Bufo marinus. The sulfidopeptide leukotrienes, LTC4, LTD4, and LTE4 elicited hypotension with equal potency. However, with respect to heart rate changes and duration of action, the responses to LTC4 and LTD4 were greater and lasted longer than those to LTE4. The nonpeptide leukotriene, LTB4, had significantly less potent effects on heart rate and blood pressure. The leukotriene-induced increases in heart rate with 1000 and 300 ng/kg body wt LTC4 and LTD4 were blocked with 5 mg/kg body wt propranolol, a beta-antagonist, suggesting sympathetic reflex regulation of heart rate. Metabolism of [3H]LTC4 to [3H]LTD4 and [3H]LTE4 occurred rapidly in blood, with complete conversion to [3H]LTE4 within 5 min. Conversion was slower in plasma, with 18.9 +/- 0.5% of the radioactivity associated with [3H]LTC4 still remaining after 120 min. The toad is more similar to mammals than the bullfrog with respect to the metabolism of leukotrienes. In contrast to mammals, leukotrienes have hypotensive effects in both toad and bullfrog, although the order of potency differs. The effectiveness of the sulfidopeptide leukotrienes in eliciting hypotension at low doses (1 ng/kg body wt) suggests that these compounds may be important cardiovascular regulators in the toad.

Tissue distribution, elimination and metabolism of [3H]-leukotriene C4 in the American bullfrog, Rana catesbeiana.

Tissue distribution, elimination, and metabolism of [3H]-leukotriene C4 were studied at 2.5 hours after injection in the conscious and anesthetized American bullfrog, Rana catesbeiana. Conscious frogs were injected via the dorsal lymph sac or the sciatic vein. Anesthetized frogs were injected via the abdominal vein. The organs containing the greatest percent of injected radioactivity at 2.5 hours after injection were liver, small intestine and kidney. Route of injection and anesthesia appears to alter distribution and elimination of leukotrienes. [3H]-leukotrienes were eliminated into bladder water and bile. In addition, 7.8 +/- 2.2 and 5.2 +/- 2.5 percent of the injected radioactivity was found in the pan water bathing the ventral surface of the venously and dorsally injected conscious frogs, respectively, suggesting transfer of radioactivity across the skin. At 2.5 hours, polar metabolites represented 50% of the radioactivity found in liver, bile, and bladder water. These polar metabolites were determined to be 18-carboxy-19,20-dinor-leukotriene E4, 20-carboxy-leukotriene E4, and 20-hydroxy-leukotriene E4. Of the non-oxidized leukotrienes, bile contained mainly LTD4 while bladder water contained primarily LTE4. N-acetyl LTE4 was not detected in any samples. The tissue distribution, elimination and metabolism of leukotrienes in the bullfrog was similar to mammalian studies and suggests evolutionary conservation of leukotriene processing.

Tissue distribution, elimination, and metabolism of [3H]leukotriene C4 by the conscious marine toad, Bufo marinus.

Tissue distribution, elimination, and metabolism of 3H-labelled leukotriene (LT) C4 were studied in ureter-catheterized conscious marine toads, Bufo marinus. Six and 24 h after injection, organs containing the highest percent of injected radioactivity were small intestine, liver, and kidney. Radioactivity declined in these organs at 24 h by approximately threefold. Peak elimination time for radioactivity in the urine was between 2 and 4 h after the injection. During the 24-h collection period, 55.2 +/- 0.2% of the injected radioactivity was eliminated in the urine. Polar metabolites represented 40.3 +/- 1.1, 57.3 +/- 5.6, and 62.8 +/- 1.6% of the radioactivity at 2, 4, and 6 h, respectively. The primary urinary polar metabolite was 20-carboxy-LTE4, with 18-carboxydinor-LTE4 and 20-hydroxy-LTE4 also present. [3H]LTE4 decreased from 37.2 +/- 1.8% at 2 h to 15.8 +/- 3.3 and 15.0 +/- 2.1% of the radioactivity at 4 and 6 h, respectively. Bile radioactivity was low. N-Acetyl-LTE4 was not detected in urine or bile samples. Radioactivity in the pan water was 14.3 +/- 2.4 and 15.8 +/- 2.5% of the injected radioactivity, at 6 and 24 h, respectively, suggesting that the skin was a route for excretion of leukotrienes. The marine toad is an interesting model demonstrating both similarities and differences from mammals in distribution, elimination, and metabolism of peptide leukotrienes.