Dihomo-prostaglandins and -thromboxane. A prostaglandin family from adrenic acid that may be preferentially synthesized in the kidney.
Arachidonic acid (5,8,11,14-eicosatetraenoic acid), the 20-carbon precursor for prostaglandin synthesis, is present in membrane lipids throughout the body and its metabolic enzyme is ubiquitously distributed.It was previously shown that adrenal glands, testis, brain, and kidney medulla contain both arachidonic acid and its chain-elongated product adrenic acid (7,10,13,16-docosatetraenoic acid).We prepared [1-14C]-adrenic acid and found that the renal medulla was the only rabbit tissue tested which readily metabolized the 22-carbon fatty acid.The major renal medullary cell type that contains adrenic acid is the renomedullary interstitial cell which we found active in converting this fatty acid into la,lbdihomo-prostaglandin Ez.Furthermore, the renomedullary cells possess recognition sites for the la,lbdihomo-prostaglandin Ez which results in an activation of adenylate cyclase when added to these cells.The renal medullary conversion of adrenic acid to dihomoprostaglandins was greatly facilitated in microsomes prepared from the ureter-obstructed (hydronephrotic) kidney.The eight major products generated by the hydronephrotic kidney were purifed by high performance liquid chromatography and upon analysis by gas chromatography-mass spectrometry were shown to be la,lb-dihomo-8-keto-prostaglandin F1, (the dihomoprostacyclin metabolite), la,lb-dihomo-thromboxane Bz, la,lb-dihomo-prostaglandin Fz,, la,lb-dihomoprostaglandin Ez, la,lb-dihomo-prostaglandin Dz, two 14-hydroxynonadecatrienoic acids (the other metabolite of thromboxane synthetase), and 13-hydroxydocosatetraenoic acid.The limited distribution of adrenic acid and the demonstrated ability of the rabbit renal medulla to metabolize this fatty acid create the possi- bility for a family of prostaglandin metabolites largely restricted to the kidney.The essential fatty acid linoleic acid (18:2) is sequentially desaturated and chain elongated to form arachidonic acid (204, 5,8,11,14-eicosatetraenoic acid), the precursor of prostaglandin (of the two series), thromboxane, and lipoxygenase products.Adrenal glands, brain, testis, and the renomedullary interstitial cells of the kidney medulla contain a significant amount of 7,10,13,16-docosatetraenoic acid (22:4) which is