Sphingosine and psychosine, suggested inhibitors of protein kinase C, inhibit LH effects in rat luteal cells

The possible involvement of protein kinase C on luteinizing hormone (LH) effects in dispersed rat luteal cells was investigated using two substances that have been reported to be protein kinase C inhibitors, sphingosine and psychosine. Sphingosine efficiently inhibited protein kinase C activity both...

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Veröffentlicht in:Molecular and cellular endocrinology 1988-12, Vol.60 (2), p.127-135
Hauptverfasser: Sender Baum, Monica G., Ahrén, Kurt E.B.
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description The possible involvement of protein kinase C on luteinizing hormone (LH) effects in dispersed rat luteal cells was investigated using two substances that have been reported to be protein kinase C inhibitors, sphingosine and psychosine. Sphingosine efficiently inhibited protein kinase C activity both in brain and luteal cytosol fractions. Both substances inhibited LH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in a dose-dependent fashion with an ID 50 at 3–7 μM (sphingosine) and 40 μ.m (psychosine). LH-stimulated progesterone production was also inhibited with an ID 50 at 6–10 μM (sphingosine) and 40–100 μM (psychosine). The inhibition was not due to an increased phosphodiesterase activity since IBMX (3-isobutyl-1-methylxanthine, 0.1 mM) and RO 20–1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, 0.1 mM) did not abolish the inhibitory effect of sphingosine. To study the mode of action of sphingosine, forskolin and cAMP analogues were tested. The effect of these substances on Steroidogenesis was inhibited, as well as the forskolin-induced cAMP accumulation, by sphingosine. This study demonstrates a clear inhibition of LH-stimulated effects by sphingosine and psychosine. LH action in rat luteal cells is discussed in relation to protein kinase C and the possible mode of sphingosine action.
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Sphingosine efficiently inhibited protein kinase C activity both in brain and luteal cytosol fractions. Both substances inhibited LH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in a dose-dependent fashion with an ID 50 at 3–7 μM (sphingosine) and 40 μ.m (psychosine). LH-stimulated progesterone production was also inhibited with an ID 50 at 6–10 μM (sphingosine) and 40–100 μM (psychosine). The inhibition was not due to an increased phosphodiesterase activity since IBMX (3-isobutyl-1-methylxanthine, 0.1 mM) and RO 20–1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, 0.1 mM) did not abolish the inhibitory effect of sphingosine. To study the mode of action of sphingosine, forskolin and cAMP analogues were tested. The effect of these substances on Steroidogenesis was inhibited, as well as the forskolin-induced cAMP accumulation, by sphingosine. This study demonstrates a clear inhibition of LH-stimulated effects by sphingosine and psychosine. 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Sphingosine efficiently inhibited protein kinase C activity both in brain and luteal cytosol fractions. Both substances inhibited LH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in a dose-dependent fashion with an ID 50 at 3–7 μM (sphingosine) and 40 μ.m (psychosine). LH-stimulated progesterone production was also inhibited with an ID 50 at 6–10 μM (sphingosine) and 40–100 μM (psychosine). The inhibition was not due to an increased phosphodiesterase activity since IBMX (3-isobutyl-1-methylxanthine, 0.1 mM) and RO 20–1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, 0.1 mM) did not abolish the inhibitory effect of sphingosine. To study the mode of action of sphingosine, forskolin and cAMP analogues were tested. The effect of these substances on Steroidogenesis was inhibited, as well as the forskolin-induced cAMP accumulation, by sphingosine. This study demonstrates a clear inhibition of LH-stimulated effects by sphingosine and psychosine. LH action in rat luteal cells is discussed in relation to protein kinase C and the possible mode of sphingosine action.</description><subject>1-Methyl-3-isobutylxanthine - pharmacology</subject><subject>4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology</subject><subject>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Bucladesine - pharmacology</subject><subject>Colforsin - pharmacology</subject><subject>Corpus Luteum - metabolism</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP - biosynthesis</subject><subject>Cytosol - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Luteal Cells - drug effects</subject><subject>Luteal Cells - metabolism</subject><subject>Luteinizing hormone</subject><subject>Luteinizing Hormone - antagonists &amp; inhibitors</subject><subject>Luteinizing Hormone - pharmacology</subject><subject>Progesterone - biosynthesis</subject><subject>Protein kinase C</subject><subject>Protein Kinase C - antagonists &amp; inhibitors</subject><subject>Psychosine</subject><subject>Psychosine - pharmacology</subject><subject>Rat luteal cells</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Sphingosine</subject><subject>Sphingosine - analogs &amp; derivatives</subject><subject>Sphingosine - pharmacology</subject><subject>Steroidogenesis</subject><subject>Vertebrates: endocrinology</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAQtRBVWVr-AUi-gEBqih3bsXNBQqt-IK3EAThbXnu8a8g6iydB6r8n6S7trRxG1sx78_T8hpDXnF1yxpuPTDBR6Zrp98Z8aBnXvKqfkQU3uq4MU_o5WTxQXpCXiD8ZY1rV5pSc1rIRrRQL0n3bb1Pe9JgyUJcD3eOd3963FxTHzQZwgEBT3qZ1GvqCtI90X_oBUqa_UnYIdHnxD6erWwoxgh9wGtHiBtqNA7iOeug6PCcn0XUIr47vGflxffV9eVutvt58WX5eVV5yM1RORalapVgTQhRzRe9qwZVTOqx503ilFZOKmxj5uuGi1dIwZwQAN8oEcUbeHXQno7_H6Qd2l3B24DL0I1ptmloozf5L5IpLI1kzEeWB6EuPWCDafUk7V-4sZ3a-hp2jtnPU1hh7fw1bT2tvjvrjegfhYekY_4S_PeIOveticdknfNRudWt0O_v8dODBlNqfBMWiT5A9hFSmsG3o09NG_gIr_qXH</recordid><startdate>19881201</startdate><enddate>19881201</enddate><creator>Sender Baum, Monica G.</creator><creator>Ahrén, Kurt E.B.</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>19881201</creationdate><title>Sphingosine and psychosine, suggested inhibitors of protein kinase C, inhibit LH effects in rat luteal cells</title><author>Sender Baum, Monica G. ; Ahrén, Kurt E.B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-a5f4595506ddf3ddf3fca2315a57db166c57504518ff1b61397480a83ee1858d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>1-Methyl-3-isobutylxanthine - pharmacology</topic><topic>4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology</topic><topic>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Bucladesine - pharmacology</topic><topic>Colforsin - pharmacology</topic><topic>Corpus Luteum - metabolism</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP - biosynthesis</topic><topic>Cytosol - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Luteal Cells - drug effects</topic><topic>Luteal Cells - metabolism</topic><topic>Luteinizing hormone</topic><topic>Luteinizing Hormone - antagonists &amp; inhibitors</topic><topic>Luteinizing Hormone - pharmacology</topic><topic>Progesterone - biosynthesis</topic><topic>Protein kinase C</topic><topic>Protein Kinase C - antagonists &amp; inhibitors</topic><topic>Psychosine</topic><topic>Psychosine - pharmacology</topic><topic>Rat luteal cells</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Sphingosine</topic><topic>Sphingosine - analogs &amp; derivatives</topic><topic>Sphingosine - pharmacology</topic><topic>Steroidogenesis</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sender Baum, Monica G.</creatorcontrib><creatorcontrib>Ahrén, Kurt E.B.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sender Baum, Monica G.</au><au>Ahrén, Kurt E.B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sphingosine and psychosine, suggested inhibitors of protein kinase C, inhibit LH effects in rat luteal cells</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>1988-12-01</date><risdate>1988</risdate><volume>60</volume><issue>2</issue><spage>127</spage><epage>135</epage><pages>127-135</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><coden>MCEND6</coden><abstract>The possible involvement of protein kinase C on luteinizing hormone (LH) effects in dispersed rat luteal cells was investigated using two substances that have been reported to be protein kinase C inhibitors, sphingosine and psychosine. Sphingosine efficiently inhibited protein kinase C activity both in brain and luteal cytosol fractions. Both substances inhibited LH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in a dose-dependent fashion with an ID 50 at 3–7 μM (sphingosine) and 40 μ.m (psychosine). LH-stimulated progesterone production was also inhibited with an ID 50 at 6–10 μM (sphingosine) and 40–100 μM (psychosine). The inhibition was not due to an increased phosphodiesterase activity since IBMX (3-isobutyl-1-methylxanthine, 0.1 mM) and RO 20–1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, 0.1 mM) did not abolish the inhibitory effect of sphingosine. To study the mode of action of sphingosine, forskolin and cAMP analogues were tested. The effect of these substances on Steroidogenesis was inhibited, as well as the forskolin-induced cAMP accumulation, by sphingosine. This study demonstrates a clear inhibition of LH-stimulated effects by sphingosine and psychosine. LH action in rat luteal cells is discussed in relation to protein kinase C and the possible mode of sphingosine action.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>2463943</pmid><doi>10.1016/0303-7207(88)90171-2</doi><tpages>9</tpages></addata></record>
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ispartof Molecular and cellular endocrinology, 1988-12, Vol.60 (2), p.127-135
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subjects 1-Methyl-3-isobutylxanthine - pharmacology
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology
8-Bromo Cyclic Adenosine Monophosphate - pharmacology
Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Bucladesine - pharmacology
Colforsin - pharmacology
Corpus Luteum - metabolism
Cyclic AMP
Cyclic AMP - biosynthesis
Cytosol - metabolism
Dose-Response Relationship, Drug
Female
Fundamental and applied biological sciences. Psychology
Luteal Cells - drug effects
Luteal Cells - metabolism
Luteinizing hormone
Luteinizing Hormone - antagonists & inhibitors
Luteinizing Hormone - pharmacology
Progesterone - biosynthesis
Protein kinase C
Protein Kinase C - antagonists & inhibitors
Psychosine
Psychosine - pharmacology
Rat luteal cells
Rats
Rats, Inbred Strains
Sphingosine
Sphingosine - analogs & derivatives
Sphingosine - pharmacology
Steroidogenesis
Vertebrates: endocrinology
title Sphingosine and psychosine, suggested inhibitors of protein kinase C, inhibit LH effects in rat luteal cells
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