PGE2, forskolin, and cholera toxin interactions in modulating NaCl transport in mouse mTALH.
Prostaglandin E2 (PGE2) inhibits the ADH-stimulated components of the lumen-positive transepithelial voltage (Ve) and of net chloride absorption (JnetCl) in the isolated microperfused mouse medullary thick ascending limb of Henle (mTALH), presumably by interfering with the ADH-dependent intracellular accumulation of cAMP. These experiments examined the interactions of PGE2 with two nonhormonal stimulators of adenylate cyclase--cholera toxin and forskolin--in an attempt to evaluate the means by which PGE2 inhibits ADH-stimulated transport in these mTALH segments. Forskolin (FSK) stimulated Ve in the mTALH with half-maximal stimulation at 1.4 X 10(-7) M FSK. PGE2 had no effect on FSK stimulation of Ve; 10(-6) M FSK reversed completely the PGE2 inhibition of ADH-stimulated Ve. A low concentration of cholera toxin, 5 X 10(-13) M, stimulated Ve and JnetCl in the mTALH; 10(-6) M PGE2 inhibited the stimulation by cholera toxin; and 10(-6) M FSK reversed the PGE2 inhibition of both Ve and JnetCl in cholera toxin-stimulated mTALH. A higher concentration of cholera toxin, 10(-10) M, stimulated Ve and JnetCl to values identical to those seen with maximal concentrations of ADH, but PGE2 did not inhibit the increments in either Ve or JnetCl produced by 10(-10) M cholera toxin. PGE2 appears to inhibit ADH stimulation of NaCl transport in mTALH by an action distal to hormone-receptor interactions yet proximal to the catalytic subunit of adenylate cyclase.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone; D004224:Diterpenes / Q000494:pharmacology*; D004347:Drug Interactions; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008138:Loop of Henle / Q000378:metabolism*; D008297:Male; D051379:Mice; D011458:Prostaglandins E / Q000494:pharmacology*; D012965:Sodium Chloride / Q000378:metabolism*; D013268:Stimulation, Chemical; D014667:Vasopressins / Q000494:pharmacology
D002712:Chlorides; D004224:Diterpenes; D007473:Ion Channels; D011458:Prostaglandins E; D014667:Vasopressins; D005576:Colforsin; D012965:Sodium Chloride; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone