Prostaglandin E production and hypercalcaemia in rats bearing the Walker carcinosarcoma.
The hypothesis that there is prostaglandin-mediated hypercalcaemia associated with the Walker carcinosarcoma in the rat was tested by measuring PGE production during the development of the hypercalcaemia, and determining the effects of inhibition of prostaglandin synthesis on serum calcium concentration. Parathyroid hormone (PTH) activity was estimated by the determination of the serum concentration of immunoreactive PTH. There was a 3-fold increase in the urinary excretion of 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid (PGE-M), a major urinary metabolite of the E prostaglandins from basal levels. Treatment with indomethacin, a potent inhibitor of prostaglandin synthesis, did not lower serum calcium concentrations with two different doses (1·6 mg/kg/day orally and 5 mg/kg/day i.m.); effective inhibition of prostaglandin synthesis was demonstrated by the suppression of PGE-M excretion rates below basal levels. Serum concentrations of immunoreactive PTH were not significantly altered by either tumour growth or indomethacin. Dexamethasone (0·5 mg/kg/day i.m.) attenuated both the increased urinary excretion of PGE-M and the rise in serum calcium concentration, suggesting that one or several lipoxygenase products might be the actual mediators of the hypercalcaemia. We conclude that the hypercalcaemia in the rat with Walker carcinosarcoma is probably not mediated by E-prostaglandins and probably not by any other product of the cyclo-oxygenase pathway. The increased PGE turnover may be considered as a biochemical marker of tumour load, but not as an indicator of a prostaglandin-mediated hypercalcaemia.
D000818:Animals; D002118:Calcium / Q000097:blood; D002279:Carcinoma 256, Walker / Q000150:complications / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000097:blood; D011458:Prostaglandins E / Q000652:urine*; D051381:Rats
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D003907:Dexamethasone; D002118:Calcium; D007213:Indomethacin