Effect of pH on the permeability of the distal nephron to prostaglandins E2 and F2 alpha.
Because PGE2 and F2 alpha are derivatives of arachidonic acid, the effect of pH on dissociation of the carboxyl group would be expected to alter the lipid solubility of these substances and consequently their efflux from the distal nephron. To assess this possibility on the single nephron level, 20-nl samples of chromatographically pure [3H]prostaglandins were microinjected into early distal tubules and their recovery was compared with that of [14C]insulin in rats undergoing osmotic diuresis with NaHCO3 or Na2SO4 containing HCl. Although urine flow rates were similar, there was a striking elevation of urine pH in bicarbonate-loaded rats (7.87 +/- 0.017 vs. 5.66 +/- 0.067). To examine luminal factors acting on prostaglandin movement, collections of early distal fluid were made and total [CO2] was measured by microcalorimetry. There was no difference in distal flow rate, whereas total [CO2] and calculated pH were significantly elevated in the bicarbonate-loaded rats (7.66 +/- 0.029 vs. 6.07 +/- 0.093). We found that tubular efflux of both prostaglandins from the distal nephron is very small as the maximum efflux measured in acid-loaded rats was only 4% of the injected quantity. However, there was no efflux of PGE2 when microinjection was made into distal tubules of bicarbonate-loaded animals. All isotope excreted in the urine was the unchanged parent prostaglandin and both prostaglandins were coexcreted with inulin for all injections in bicarbonate- and acid-loaded animals. These results suggest that permeability of the distal nephron to PGE2 and F2 alpha is normally very low. Nevertheless, permeability of PGE2 can be further reduced when urine pH is elevated.
D000136:Acid-Base Equilibrium; D000818:Animals; D006863:Hydrogen-Ion Concentration; D008297:Male; D009399:Nephrons / Q000378:metabolism*; D010539:Permeability; D011458:Prostaglandins E / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011458:Prostaglandins E; D011460:Prostaglandins F