title: PGE2 inhibits water permeability at a post-cAMP site in rat terminal inner medullary collecting duct.
abstract: To assess sites and mechanism of action of prostaglandin E2 (PGE2) on water permeability (PF), we determined PGE2 effects on antidiuretic hormone (ADH)- and adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated PF in rat terminal inner medullary collecting ducts perfused in vitro. PGE2 (10(-7) M) reversibly inhibited ADH-stimulated PF (1.131 +/- 192 to 532 +/- 208 microns/s). In contrast to that observed in rabbit, PGE2 also inhibited an established PF response to the exogenous cAMP analogue 8-p-(chlorophenylthio)-cAMP (696 +/- 107 to 399 +/- 99 microns/s). PGE2 alone had no effect on PF. The protein kinase C inhibitor staurosporine (10(-8) M) blocked PGE2-mediated inhibition of cAMP-stimulated PF. PGE2 caused a rapid spikelike increase in intracellular calcium [( Ca2+]i) followed by a stable elevation above basal values. Only the latter effect was abolished in a zero calcium bath. Neither staurosporine nor cAMP altered the [Ca2+]i response. These studies are the first to demonstrate PGE2-mediated inhibition of an established PF response to cAMP independent of changes in intracellular cAMP. The pattern of [Ca2+]i release and sensitivity to staurosporine suggests that this effect is mediated via signaling through phospholipase C. The results underscore the importance of species differences, axial heterogeneity, and/or in vivo conditioning for functional expression of cellular signaling pathways.
authors.affiliation: Department of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: S P
authors.initials: SP
authors.lastname: Nadler
authors.forename: J A
authors.initials: JA
authors.lastname: Zimpelmann
authors.forename: R L
authors.initials: RL
authors.lastname: Hébert
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D010539:Permeability / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D014667:Vasopressins / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D014867:Water; D014667:Vasopressins; D000242:Cyclic AMP; D011493:Protein Kinase C; D019311:Staurosporine; D015232:Dinoprostone; D002118:Calcium