TY - JOUR
T1 - Synthesis of prostaglandins by the rat renal papilla in vitro. Mechanism of stimulation by angiotensin II
AU - Danon, Abraham
AU - Chang, Lucas C.T.
AU - Sweetman, Brian J.
AU - Nies, Alan S.
AU - Oates, John A.
N1 - Funding Information:
This work was supported in part by NIH Grants GM 15431 and HL 16489. We wish to thank Drs John E. Pike and Udo Axen, The Upjohn Company, Kalamazoo, Michigan for the prostaglandins and deuterated analogues. We are grateful to Mrs Cynthia Dugger for capable technical assistancea nd to Dr Kenneth A. Aulsebrook who carried out many of the bioassays.P art of this study was performed with A.D. under tenure of a Merck Foundation International Fellowship in Clinical Pharmacology. A.S.N. is a recipient of the Pharmaceutical Manufacturers Association Foundation Faculty Development Award.
PY - 1975/4/18
Y1 - 1975/4/18
N2 - 1. 1. The biosynthesis of prostaglandins in the rat renal papilla was studied in a whole-cell preparation in vitro. Prostaglandins recovered from the incubation medium were identified by gas chromatography-mass spectrometry as prostaglandin E2 and prostaglandin F2α. Quantitative estimates of prostaglandin output were obtained by bioassay and confirmed by selected ion monitoring. 2. 2. Prostaglandin biosynthesis was enhanced by exogenous arachidonic acid and also by triglyceride lipase, indicating that arachidonic acid released from papillary triglycerides is readily available for prostaglandin biosynthesis. 3. 3. Angiotensin II (10-100 ng/ml) stimulated the biosynthesis of both prostaglandin E2 and prostaglandin F2α, thus increasing prostaglandin levels in both the incubation medium and the tissues. 4. 4. The mechanism whereby angiotensin II stimulates prostaglandin biosynthesis was investigated using the isotope dilution technique. In the presence of [14C]-arachidonic acid, angiotensin II stimulated the output of more prostaglandin that had a significantly lower specific activity than the controls. Angiotensin II therefore increased the availability of endogenous, non-labelled substrate for prostaglandin biosynthesis. This conclusion was supported by experiments in which enough arachidonic acid was added to make the kinetics of prostaglandin synthesis zero order. Under such conditions angiotensin II failed to cause any further increase in prostaglandin synthesis. 5. 5. It is concluded that angiotensin II controls prostaglandin biosynthesisin the renal papilla by regulating the availability of free precursor. Possible mechanisms for increased levels of free arachidonic acid could be the activation of a tissue acyl hydrolase or decreased utilization of fatty acids.
AB - 1. 1. The biosynthesis of prostaglandins in the rat renal papilla was studied in a whole-cell preparation in vitro. Prostaglandins recovered from the incubation medium were identified by gas chromatography-mass spectrometry as prostaglandin E2 and prostaglandin F2α. Quantitative estimates of prostaglandin output were obtained by bioassay and confirmed by selected ion monitoring. 2. 2. Prostaglandin biosynthesis was enhanced by exogenous arachidonic acid and also by triglyceride lipase, indicating that arachidonic acid released from papillary triglycerides is readily available for prostaglandin biosynthesis. 3. 3. Angiotensin II (10-100 ng/ml) stimulated the biosynthesis of both prostaglandin E2 and prostaglandin F2α, thus increasing prostaglandin levels in both the incubation medium and the tissues. 4. 4. The mechanism whereby angiotensin II stimulates prostaglandin biosynthesis was investigated using the isotope dilution technique. In the presence of [14C]-arachidonic acid, angiotensin II stimulated the output of more prostaglandin that had a significantly lower specific activity than the controls. Angiotensin II therefore increased the availability of endogenous, non-labelled substrate for prostaglandin biosynthesis. This conclusion was supported by experiments in which enough arachidonic acid was added to make the kinetics of prostaglandin synthesis zero order. Under such conditions angiotensin II failed to cause any further increase in prostaglandin synthesis. 5. 5. It is concluded that angiotensin II controls prostaglandin biosynthesisin the renal papilla by regulating the availability of free precursor. Possible mechanisms for increased levels of free arachidonic acid could be the activation of a tissue acyl hydrolase or decreased utilization of fatty acids.
UR - http://www.scopus.com/inward/record.url?scp=0016682317&partnerID=8YFLogxK
U2 - 10.1016/0005-2760(75)90063-6
DO - 10.1016/0005-2760(75)90063-6
M3 - Article
AN - SCOPUS:0016682317
VL - 388
SP - 71
EP - 83
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
SN - 1388-1981
IS - 1
ER -