Subcellular Localization of the Prostaglandin System in the Rabbit Renal Papilla

Abstract

ANGG~RD, E., S. 0. BOHMAN, J. E. GRIFFIN 111, C. LARSSON and A. B. MAUNS-BACH. Subcellular localization of the prostaglandin system in the rabbit renal papilla. Acta physiol. scand. 1972. 84. 231-246. The occurrence of prostaglandins (PG), prostaglandin precursor acids, prostaglandin synthetase and 15-hydroxy prostaglandin dehydrogenase was studied in subcellular fractions isolated from homogenates of rabbit renal papilla by sucrose density gradient centrifugation. The investigated fractions were lipid droplets, supernatant, microsomes and mitochondria as verified by electron microscopy. Most of the prostaglandins was found to be prostaglandin E2 and was present in the supernatant whereas the prostaglandin synthetase occurred most abundantly in the micro-soma1 fraction: Nearly all of the recovered prostaglandins were formed during the preparation of the subcellular fractions. Arachidonic acid was the major esterified Czo acid and had the highest relative concentrations in the supernatant, microsomes, and mitochondria, whereas the lipid droplets had lower concentrations. No detectable 15-hydroxy prostaglandin dehydrogenase was present in the supernatant fraction of the papilla. The results indicate that in the rabbit renal papilla prostaglandin E2 is formed mainly from locally available arachidonate in membranes which sediment in the microsomal fraction and which may be derived from either cell membranes or membranes of the endoplasmic reticulum. After their formation the prostaglandins are probably released into the cytoplasm of the cells rather than being concentrated within specific subcellular particles and may leave the papilla without undergoing metabolic inactivation.The original discovery that the renal medulla contains appreciable quantities of prostaglandin-like material (Lee et al. 1965) has since been extended in several directions. The major prostaglandin was identified as prostaglandin E2 (Daniels et al. 1967, Lee et al. 1967 or closely related compounds. The biosynthesis of PGEfrom 3H-labelled arachidonic acid was demonstrated in rabbit renal medulla by Hamberg (1969). PGEz was observed to be released in renal venous blood after ischemia (McGiff et al. 1970 a, Edwasds, Strong and fiunt 1969), nerve stimulation (Dunham and Zimmerman, 1970) angiotensin (McGiff et al. 1970 b) and into renaI lymph following injection of noradrenaline (Fujimoto and Lockett 1969). 23 1 232 E. X N G G h D ET AL.Since prostaglandin E-compounds antagonize the actions of antidiuretic hormone (Orloff, Handler and Bergstrom 1965, Orloff and Grantham 1966, Johnston, Herzog and Lauler 1967 and have strong natriuretic effects (Herzog, Johnston and Lauler 1966, Johnston et al. 1967 b) a physiological role has been suggested for PGE-as an intrarenal modulator of salt and water excretion.The interstitial cells of the renal medulla contain numerous lipid droplets and have been assigned secretory functions (Gloor and Xeiditsch-Halff 1965, Bulger and Trump 1966. Osvaldo and Latta 1966. Nissen 1967. The lipid droplets accumulate dur...

Renal prostaglandin synthesis in the spontaneously hypertensive rat.

“…There is general agreement that prostaglandins are not stored within cells (23)(24)(25)(26). Prostaglandin synthesis is rapid, apparently limited by substrate availability and hence turnover is extensive.…”

“…These precautions may explain why the values in Table I are much lower than previously reported (5). Therefore if appropriate care is taken to avoid significant postmortem tissue synthesis, tissue levels are quite low and may be a poor reflection of in vivo synthesis (23).…”

Urinary prostaglandins. Identification and origin.

“…1 Abbreviationis used in this paper: CPBA, competitive cating little direct excretory clearance of the primary prostaglandins from the circulation. The kidney itself, however, is a prime site of prostaglandin synthesis (3)(4)(5), and it was conceived that PG synthesized in the kidney might diffuse directly into the urine. Certainly some substances such as tryptamine (6) and cyclic AMP (7) appear in the urine totally or in part as a reflection of their intrarenal synthesis.…”

Effect of bumetanide, frusemide and prostaglandin E2 on the isolated perfused kidney of rat and rabbit

“…Initially it was believed that their activity was largely confined to the renal papilla and medulla where all species studied showed a rich source of prostaglandin synthetase (Anggard et al, 1972;Crowshaw & McGiff, 1973;Larsson & Anggard 1973;Blackwell et al, 1975;Dunn 1976). However, it was also shown that the renal cortex could synthesize small amounts of prostaglandin E2 (PGE2) and PGF2,,: (Larsson et al, 1974;Dunn 1976;Pong & Levine 1976).…”