RENAL BIOSYNTHESIS OF PROSTAGLANDIN-E2 AND F2-ALPHA - DEPENDENCE ON EXTRACELLULAR POTASSIUM

  • 1 January 1978
    • journal article
    • research article
    • Vol. 92  (5) , 669-677
Abstract
Since recent investigations have shown elevated urinary PG[prostaglandin]E2 and polyuria in hypokalemic animals which were reversed by PG synthesis inhibition with indomethacin, studies examined the effects of extracellular [K+] on renomedullary PG production in vitro. Slices of rabbit and human renal papilla were incubated in Krebs-Ringer .**GRAPHIC**. buffer, 95% O2-5% CO2, glucose 10 mM, HSA [human serum albumin] 4 gm/100 ml, for 30 min at 38.degree. C, with and without 1-14C-AA [arachidonic acid] (10 .mu.M). Measurements were made of total endogenous i[immunoreactive]PGE2 and iPGF2.alpha. production and radioactive AA .fwdarw. PGE2. In rabbit renal medulla values for iPGE2 (nmol/g per 30 min) were 252 .+-. 20 at [K+] 0, 182 .+-. 17 at [K+] 2.5 meq/l, 163 .+-. 18 at [K+] 5.5 and 129 .+-. 17 [K+] 9.0 (P < 0.005). iPGF2.alpha. was unaltered by changes in media K concentrations (6.8 .+-. 0.9 nmol/g per 30 min at [K+] 0 and 6.2 .+-. 0.8 at [K+] 9.0 meq/l. In the human renal medulla iPGE2 was 9.5 .+-. 1.6 nmol/g per 30 min at [K+] 0, 5.0 .+-. 0.7 at [K+] 2.5 meq/l, 5.3 .+-. 0.3 at [K+] 5.5 and 4.6 .+-. 1.0 at [K+] 9.0 (P < 0.05). AA .fwdarw. PGE2 (nmol/g per 30 min) was 3.21 .+-. 0.92 at [K+] 0, 2.47 .+-. 0.57 at [K+] 2.5 meq/l, 1.30 .+-. 0.30 at [K+] 5.5 and 0.76 .+-. 0.40 at [K+] 9.0 in rabbit renal medulla (P < 0.005). Direct stimulation of papillary PGE2 biosynthesis by low extracellular [K+] impairing the c[cyclic]AMP-generating response to vasopressin could represent the initial event in the pathogenesis of vasopressin-resistant polyuria.