Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells

Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells. The effects of lithium (Li) on the cAMP system in rat inner medullary collecting tubule cells were studied. While acute exposure to 5mM Li was without effect, 10mM, 25mM and 50mM Li significantly decreased...

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Veröffentlicht in:Kidney international 1990-05, Vol.37 (5), p.1211-1218
Hauptverfasser: Anger, Michael S., Shanley, Paul, Mansour, Julie, Berl, Tomas
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Shanley, Paul
Mansour, Julie
Berl, Tomas
description Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells. The effects of lithium (Li) on the cAMP system in rat inner medullary collecting tubule cells were studied. While acute exposure to 5mM Li was without effect, 10mM, 25mM and 50mM Li significantly decreased AVP-stimulated cAMP formation. In contrast, cells grown in 5mM Li for 72hours which caused no morphologic changes enhanced cAMP formation (fmol/μg protein) in response to both 10nM AVP (114.5 ± 9.2 vs. 71.6 ± 7.4,P > 0.005) and 100nM AVP (182 ± 14 vs. 120 ± 8.3, P < 0.001), N = 16. A similar enhancement was observed when cAMP formation was stimulated by a post-receptor agonist, cholera toxin. The role of eicosanoids was examined with 5 μM meclofenamate which reversed Li-enhanced cAMP formation in response to both AVP and cholera toxin. To define the eicosanoid responsible, cyclooxygenase products were measured. Prostaglandin E2; and thromboxane B2 synthesis were unchanged by Li, but the production of prostacyclin was significantly (P < 0.02) increased. Prostacyclin (3 μM) mimicked the effect of Li to enhance the response to 10nM AVP as cAMP levels increased from 100 ± 11 to 173 ± 13, P < 0.05. The experiments suggest that acute exposure of Li at concentrations of 10mM or greater inhibit cAMP formation but prolonged Li exposure enhances cAMP formation by increasing the formation of prostacyclin.
doi_str_mv 10.1038/ki.1990.104
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Prostacyclin (3 μM) mimicked the effect of Li to enhance the response to 10nM AVP as cAMP levels increased from 100 ± 11 to 173 ± 13, P &lt; 0.05. 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The effects of lithium (Li) on the cAMP system in rat inner medullary collecting tubule cells were studied. While acute exposure to 5mM Li was without effect, 10mM, 25mM and 50mM Li significantly decreased AVP-stimulated cAMP formation. In contrast, cells grown in 5mM Li for 72hours which caused no morphologic changes enhanced cAMP formation (fmol/μg protein) in response to both 10nM AVP (114.5 ± 9.2 vs. 71.6 ± 7.4,P &gt; 0.005) and 100nM AVP (182 ± 14 vs. 120 ± 8.3, P &lt; 0.001), N = 16. A similar enhancement was observed when cAMP formation was stimulated by a post-receptor agonist, cholera toxin. The role of eicosanoids was examined with 5 μM meclofenamate which reversed Li-enhanced cAMP formation in response to both AVP and cholera toxin. To define the eicosanoid responsible, cyclooxygenase products were measured. Prostaglandin E2; and thromboxane B2 synthesis were unchanged by Li, but the production of prostacyclin was significantly (P &lt; 0.02) increased. Prostacyclin (3 μM) mimicked the effect of Li to enhance the response to 10nM AVP as cAMP levels increased from 100 ± 11 to 173 ± 13, P &lt; 0.05. The experiments suggest that acute exposure of Li at concentrations of 10mM or greater inhibit cAMP formation but prolonged Li exposure enhances cAMP formation by increasing the formation of prostacyclin.</description><subject>Animals</subject><subject>Arginine Vasopressin - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Cholera Toxin - pharmacology</subject><subject>Cyclic AMP - biosynthesis</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Eicosanoids - biosynthesis</subject><subject>Epoprostenol - pharmacology</subject><subject>Kidney Medulla - drug effects</subject><subject>Kidney Medulla - metabolism</subject><subject>Kidney Tubules - metabolism</subject><subject>Kidney Tubules, Collecting - drug effects</subject><subject>Kidney Tubules, Collecting - metabolism</subject><subject>Lithium - pharmacology</subject><subject>Meclofenamic Acid - pharmacology</subject><subject>Medical sciences</subject><subject>Pharmacology. 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The effects of lithium (Li) on the cAMP system in rat inner medullary collecting tubule cells were studied. While acute exposure to 5mM Li was without effect, 10mM, 25mM and 50mM Li significantly decreased AVP-stimulated cAMP formation. In contrast, cells grown in 5mM Li for 72hours which caused no morphologic changes enhanced cAMP formation (fmol/μg protein) in response to both 10nM AVP (114.5 ± 9.2 vs. 71.6 ± 7.4,P &gt; 0.005) and 100nM AVP (182 ± 14 vs. 120 ± 8.3, P &lt; 0.001), N = 16. A similar enhancement was observed when cAMP formation was stimulated by a post-receptor agonist, cholera toxin. The role of eicosanoids was examined with 5 μM meclofenamate which reversed Li-enhanced cAMP formation in response to both AVP and cholera toxin. To define the eicosanoid responsible, cyclooxygenase products were measured. Prostaglandin E2; and thromboxane B2 synthesis were unchanged by Li, but the production of prostacyclin was significantly (P &lt; 0.02) increased. Prostacyclin (3 μM) mimicked the effect of Li to enhance the response to 10nM AVP as cAMP levels increased from 100 ± 11 to 173 ± 13, P &lt; 0.05. The experiments suggest that acute exposure of Li at concentrations of 10mM or greater inhibit cAMP formation but prolonged Li exposure enhances cAMP formation by increasing the formation of prostacyclin.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>2161061</pmid><doi>10.1038/ki.1990.104</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Arginine Vasopressin - pharmacology
Biological and medical sciences
Cells, Cultured
Cholera Toxin - pharmacology
Cyclic AMP - biosynthesis
Drug toxicity and drugs side effects treatment
Eicosanoids - biosynthesis
Epoprostenol - pharmacology
Kidney Medulla - drug effects
Kidney Medulla - metabolism
Kidney Tubules - metabolism
Kidney Tubules, Collecting - drug effects
Kidney Tubules, Collecting - metabolism
Lithium - pharmacology
Meclofenamic Acid - pharmacology
Medical sciences
Pharmacology. Drug treatments
Rats
Toxicity: urogenital system
title Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells
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