Prostaglandins (PGs) synthesized in the medulla, a major source of renal PGs, could have a direct effect on several tubular functions. In order to better characterize the site and pattern of PG synthesis in different medullary nephron segments, we examined PG synthesis by isolated medullary cells, a preparation enriched in medullary collecting tubule cells and isolated cells from the thick ascending limb of Henle's loop (TALH). Incubation of medullary cells and medullary collecting tubule cells in the presence of 5 μM [14C]arachidonic acid produced predominantly PGE2 with much less PGF2(α). In comparison, TALH cells synthesized only about 20% as much labeled PG composed of nearly equal amounts of PGE2 and PGF2(α). Specific radioimmunoassay after incubation in the absence of exogenous arachidonic acid revealed that medullary cells synthesized 83 ± 15 ng of PGE2/mg of protein x 15 min compared with 15 ± 5 ng of PGE2 for TALH cells. Furosemide (1 mM) inhibited PGE2 synthesis in medullary cells but had no effect on TALH cells. Bumetanide (1 mM) and amiloride (1 mM) had no effect. The calcium ionophore A23187 (2 μM) doubled PGE2 synthesis in both cell populations. The synthesis of PGF2(α) was comparable in all three preparations, but was only 5% of PGE2 production in medullary and medullary collecting tubule cells and about 20% of PGE2 production in TALH cells. Furosemide (1 mM) stimulated PGF2(α) synthesis in medullary cells and TALH cells (2.9 ± 0.7 to 6.8 ± 1.3 and 1.5 ± 0.7 to 5.5 ± 1.4 ng/mg of protein x 15 min, respectively). Hydrochlorothiazide was without effect. A23187 (2 μM) increased PGF2(α) synthesis 2- to 3-fold in both cell populations. These results indicate that cells from different nephron segments have different patterns of PG synthesis. They do not support a direct role for PGs in the action of loop diuretics, but do not rule out possible modulation of NaCl transport by PGs.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Dec 4 1982|
ASJC Scopus subject areas
- Molecular Medicine