PGE2, forskolin, and cholera toxin interactions in rabbit cortical collecting tubule.
To define further the mechanism whereby prostaglandin (PG) E2 inhibits the hydroosmotic response to ADH, we studied the interactions of PGE2 with ADH and two nonhormonal activators of adenylate cyclase, forskolin and cholera toxin, in the isolated perfused rabbit cortical collecting tubule. Forskolin increased hydraulic conductivity (LP) in a dose-dependent fashion and to a degree comparable with ADH-stimulated LP. Forskolin also augmented maximal ADH-stimulated LP, from 135 +/- 15 (SE) to 174 +/- 7 . 10(-7) cm . s-1 . atm-1. Following a 45-min lag phase, 10(-9) M cholera toxin at 37 degrees C increased LP to 107 +/- 12 . 10(-7) cm . s-1 . atm-1, a response that was stable with time. In paired studies at both 25 and 37 degrees C, PGE2 reversibly inhibited ADH-stimulated LP by 45 and 47%, respectively. However, the same protocols with PGE2 and forskolin failed to reveal any inhibitory effect of PGE2 on forskolin-stimulated LP. PGE2 reversibly inhibited cholera toxin-stimulated LP, from 124 +/- 15 to 100 +/- 15 . 10(-7) cm . s-1 . atm-1. These results support the view that PGE2 inhibits ADH-stimulated LP by inhibiting the synthesis of cAMP and suggest that this inhibition occurs at a functional site at or distal to the nucleotide regulatory protein of adenylate cyclase.
Nadler
S P
SP
Hebert
S C
SC
Brenner
B M
BM
D000818:Animals; D001834:Body Water / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D015232:Dinoprostone; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D007672:Kidney Cortex; D007684:Kidney Tubules / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects*; D010539:Permeability; D011458:Prostaglandins E / Q000494:pharmacology*; D011817:Rabbits; D013696:Temperature; D014667:Vasopressins / Q000494:pharmacology
D011458:Prostaglandins E; D014667:Vasopressins; D005576:Colforsin; D002772:Cholera Toxin; D015232:Dinoprostone