PGE2 inhibits water permeability at a post-cAMP site in rat terminal inner medullary collecting duct
Autor: | R. L. Hebert, S. P. Nadler, J. A. Zimpelmann |
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Rok vydání: | 1992 |
Předmět: |
Male
medicine.medical_specialty Vasopressin Vasopressins Physiology Biology Dinoprostone Permeability Alkaloids Internal medicine Cyclic AMP medicine Renal medulla Animals Kidney Tubules Collecting Prostaglandin E2 Protein Kinase C Kidney Medulla Kidney Water Rats Inbred Strains Intracellular Membranes Staurosporine Adenosine Rats medicine.anatomical_structure Endocrinology Mechanism of action Calcium medicine.symptom Signal transduction Antidiuretic medicine.drug |
Zdroj: | American Journal of Physiology-Renal Physiology. 262:F229-F235 |
ISSN: | 1522-1466 1931-857X |
DOI: | 10.1152/ajprenal.1992.262.2.f229 |
Popis: | 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. |
Databáze: | OpenAIRE |
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