TY - JOUR
T1 - Prostaglandin-mediated hypercalcemia in the VX2 carcinoma-bearing rabbit
AU - Seyberth, H. W.
AU - Hubbard, W. C.
AU - Oelz, O.
AU - Sweetman, B. J.
AU - Watson, J. T.
AU - Oates, J. A.
N1 - Funding Information:
This study was supported by NIH Grant GM 15431. H. W. Seyberth was supported by the Deutsche Forschungsgemeinschaft. J.A. Oates is the Joe and Morris Werthan Professor of Investigative Medicine, and J. T. Watson is a recipient of a Research Career Development Award. We thank Dr. A. Rane for the indomethacin measurements, and Gudrun Moustafa and James L. Morgan for technical assistance.
PY - 1977/8
Y1 - 1977/8
N2 - Prostaglandin biosynthesis and metabolism were studied in the VX2 carcinoma-bearing rabbit, an animal model of prostaglandin-mediated hypercalcemia. All the identification and quantification of the prostaglandins were done by gas chromatography-mass spectrometry. The tumor incubated in vitro converted exogeneous arachidonic acid principally to PGE2. Biosynthesis from endogenous precursor lipids yields mainly PGE2 and PGF2α. The 100,000 × g supernatant fluid of the tumor did not contain any metabolizing enzymes. Significant hypercalcemia developed between the first and second week after tumor implantation. The levels of the major plasma metabolite of PGE2, 15-keto-13,14-dihydro-PGE2, became elevated at one week, had risen 25-fold by the end of the second week, and at the fourth week were elevated to 256 times the pre-incubation levels. The concentration of 15-keto-13,14-dihydro-PGF2α in plasma rose in parallel but to a lesser degree. 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid, the major urinary metabolite of the E prostaglandins, was elevated two weeks after tumor implantation and rose until the fifth week. Indomethacin treatment lowered both serum calcium and the plasma level of 15-keto-13,14-dihydro-PGE2.
AB - Prostaglandin biosynthesis and metabolism were studied in the VX2 carcinoma-bearing rabbit, an animal model of prostaglandin-mediated hypercalcemia. All the identification and quantification of the prostaglandins were done by gas chromatography-mass spectrometry. The tumor incubated in vitro converted exogeneous arachidonic acid principally to PGE2. Biosynthesis from endogenous precursor lipids yields mainly PGE2 and PGF2α. The 100,000 × g supernatant fluid of the tumor did not contain any metabolizing enzymes. Significant hypercalcemia developed between the first and second week after tumor implantation. The levels of the major plasma metabolite of PGE2, 15-keto-13,14-dihydro-PGE2, became elevated at one week, had risen 25-fold by the end of the second week, and at the fourth week were elevated to 256 times the pre-incubation levels. The concentration of 15-keto-13,14-dihydro-PGF2α in plasma rose in parallel but to a lesser degree. 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid, the major urinary metabolite of the E prostaglandins, was elevated two weeks after tumor implantation and rose until the fifth week. Indomethacin treatment lowered both serum calcium and the plasma level of 15-keto-13,14-dihydro-PGE2.
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U2 - 10.1016/0090-6980(77)90177-0
DO - 10.1016/0090-6980(77)90177-0
M3 - Article
C2 - 897223
AN - SCOPUS:0017704670
VL - 14
SP - 319
EP - 331
JO - Prostaglandins
JF - Prostaglandins
SN - 0090-6980
IS - 2
ER -