Mechanism of PGE2-induced cell swelling in distal nephron segments.
The effects of prostaglandin (PG) E2 on cell swelling were studied in isolated perfused tubules of rabbit kidney. PGE2 (1 microM) added to the bath induced cell swelling by 13.4, 7.2, and 9.6% in the connecting tubule, distal convoluted tubule, and cortical collecting duct, respectively, but it had no effect on the proximal convoluted tubule and cortical thick ascending limb. The response was dose dependent in the range of 1 nM to 1 microM. PGI2 exerted a similar effect, but PGF2 alpha had no effect. The swelling was completely blocked by basolateral Na+ removal and was attenuated by bilateral Cl- removal, suggesting that the swelling was mediated by basolateral Na+ entry in association with Cl- entry. In all segments except proximal tubule, PGE2 caused an initial transient peak followed by a sustained increase in intracellular Ca2+. Intracellular Ca2+ chelation or inhibition of Ca2+ release from intracellular stores abolished the PGE2-induced cell swelling, but extracellular Ca2+ removal did not. An inhibitor of the Na(+)-Ca2+ exchanger (3',4'-dichlorobenzamil, 100 microM) in the bath completely inhibited PGE2-induced cell swelling. Neither furosemide (1 mM) nor amiloride (1 mM) added to bath abolished the response, indicating that neither Na(+)-K(+)-2Cl- cotransport nor Na(+)-H+ exchange is involved in the action of PGE2. The swelling response to PGE2 was observed even in the presence of ouabain, indicating that the effect of PGE2 is independent of Na(+)-K(+)-adenosinetriphosphatase inhibition. Nicardipine added to bath partially inhibited the swelling response.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimizu
T
T
Shionogi Research Laboratories, Osaka, Japan.
Naruse
M
M
Takeda
M
M
Nakamura
M
M
Yoshitomi
K
K
Imai
M
M
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008536:Meglumine / Q000494:pharmacology; D009399:Nephrons / Q000166:cytology / Q000187:drug effects*; D011817:Rabbits; D012964:Sodium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D002712:Chlorides; D008536:Meglumine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D002118:Calcium