Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells
The effect of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase, on the degranulation of rat peritoneal mast cells (RMC) was studied. RMC were pretreated for 48 hr with 0.1–10 μ M MPA before the cells were sensitized with IgE and triggered with specific Ag. The net a...
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| Veröffentlicht in: | Cellular immunology 1992-05, Vol.141 (2), p.508-517 |
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| creator | Mulkins, Mary A. Ng, May Lewis, Robert A. |
| description | The effect of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase, on the degranulation of rat peritoneal mast cells (RMC) was studied. RMC were pretreated for 48 hr with 0.1–10 μ
M MPA before the cells were sensitized with IgE and triggered with specific Ag. The net amount of [
3H]5-HT released from granules was decreased by 44 and 32% with 1 and 10 μ
M MPA treatment, respectively. MPA inhibition of degranulation was completely reversed by the addition of 30 μ
M guanosine to the incubation medium. There was no difference in the apparent number or affinity of IgE binding sites between control and MPA-treated RMC. MPA pretreatment also had no effect on the IgE receptor-mediated production of PGD
2 in RMC. These results suggest that depletion of intracellular GTP pools by MPA can disrupt the signaling between the IgE receptor and the secretory granules and that, under these same conditions, the release and metabolism of arachidonic acid are unaffected. |
| doi_str_mv | 10.1016/0008-8749(92)90167-N |
| format | Article |
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M MPA before the cells were sensitized with IgE and triggered with specific Ag. The net amount of [
3H]5-HT released from granules was decreased by 44 and 32% with 1 and 10 μ
M MPA treatment, respectively. MPA inhibition of degranulation was completely reversed by the addition of 30 μ
M guanosine to the incubation medium. There was no difference in the apparent number or affinity of IgE binding sites between control and MPA-treated RMC. MPA pretreatment also had no effect on the IgE receptor-mediated production of PGD
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M MPA before the cells were sensitized with IgE and triggered with specific Ag. The net amount of [
3H]5-HT released from granules was decreased by 44 and 32% with 1 and 10 μ
M MPA treatment, respectively. MPA inhibition of degranulation was completely reversed by the addition of 30 μ
M guanosine to the incubation medium. There was no difference in the apparent number or affinity of IgE binding sites between control and MPA-treated RMC. MPA pretreatment also had no effect on the IgE receptor-mediated production of PGD
2 in RMC. These results suggest that depletion of intracellular GTP pools by MPA can disrupt the signaling between the IgE receptor and the secretory granules and that, under these same conditions, the release and metabolism of arachidonic acid are unaffected.</description><subject>Animals</subject><subject>Binding Sites, Antibody</subject><subject>Biological and medical sciences</subject><subject>Cell Degranulation - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Immunobiology</subject><subject>IMP Dehydrogenase - antagonists & inhibitors</subject><subject>Mast Cells - drug effects</subject><subject>Modulation of the immune response (stimulation, suppression)</subject><subject>Mycophenolic Acid - pharmacology</subject><subject>Peritoneal Cavity - cytology</subject><subject>Prostaglandin D2 - analysis</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Serotonin - analysis</subject><subject>Signal Transduction - drug effects</subject><issn>0008-8749</issn><issn>1090-2163</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1rVDEQhoModVv9Bwq5ENGLU2dOcj5yI0ixWqjtjV6HnGTiRs6erEm20H9v1l3qXb0amHne4eVh7BXCOQL2HwBgbMZBqneqfa_qZmhunrAVgoKmxV48ZasH5Dk7zfkXAKJUcMJOUEjVIa7Y1bd7G7drWuIcLDc2OB6WdZhCybysiTv6mcyym00JceHR82QK31IKJS5kZr4xuXBL85xfsGfezJleHucZ-3H5-fvF1-b69svVxafrxkocSmPF0Ney0-hR9T14cCS9h8F3nbOyNQ5M7T55JWmcRNubUQnwCrwRo_HOizP29vB3m-LvHeWiNyHvG5iF4i7roVWoVCf-C2LfArY9VlAeQJtizom83qawMeleI-i9ar33qPcetWr1X9X6psZeH__vpg25f6GD23p_c7ybbM3sq0cb8gPWCTkMcqzYxwNGVdpdoKSzDbRYciGRLdrF8HiPP-PNmlw</recordid><startdate>19920501</startdate><enddate>19920501</enddate><creator>Mulkins, Mary A.</creator><creator>Ng, May</creator><creator>Lewis, Robert A.</creator><general>Elsevier Inc</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19920501</creationdate><title>Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells</title><author>Mulkins, Mary A. ; Ng, May ; Lewis, Robert A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-c376901b8f19660f0de4ff07f55dc42ad0a163bf94e8b326a8930f90fa38afdf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Binding Sites, Antibody</topic><topic>Biological and medical sciences</topic><topic>Cell Degranulation - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Immunobiology</topic><topic>IMP Dehydrogenase - antagonists & inhibitors</topic><topic>Mast Cells - drug effects</topic><topic>Modulation of the immune response (stimulation, suppression)</topic><topic>Mycophenolic Acid - pharmacology</topic><topic>Peritoneal Cavity - cytology</topic><topic>Prostaglandin D2 - analysis</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Serotonin - analysis</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mulkins, Mary A.</creatorcontrib><creatorcontrib>Ng, May</creatorcontrib><creatorcontrib>Lewis, Robert A.</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cellular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mulkins, Mary A.</au><au>Ng, May</au><au>Lewis, Robert A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells</atitle><jtitle>Cellular immunology</jtitle><addtitle>Cell Immunol</addtitle><date>1992-05-01</date><risdate>1992</risdate><volume>141</volume><issue>2</issue><spage>508</spage><epage>517</epage><pages>508-517</pages><issn>0008-8749</issn><eissn>1090-2163</eissn><coden>CLIMB8</coden><abstract>The effect of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase, on the degranulation of rat peritoneal mast cells (RMC) was studied. RMC were pretreated for 48 hr with 0.1–10 μ
M MPA before the cells were sensitized with IgE and triggered with specific Ag. The net amount of [
3H]5-HT released from granules was decreased by 44 and 32% with 1 and 10 μ
M MPA treatment, respectively. MPA inhibition of degranulation was completely reversed by the addition of 30 μ
M guanosine to the incubation medium. There was no difference in the apparent number or affinity of IgE binding sites between control and MPA-treated RMC. MPA pretreatment also had no effect on the IgE receptor-mediated production of PGD
2 in RMC. These results suggest that depletion of intracellular GTP pools by MPA can disrupt the signaling between the IgE receptor and the secretory granules and that, under these same conditions, the release and metabolism of arachidonic acid are unaffected.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>1349511</pmid><doi>10.1016/0008-8749(92)90167-N</doi><tpages>10</tpages></addata></record> |
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| ispartof | Cellular immunology, 1992-05, Vol.141 (2), p.508-517 |
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| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Binding Sites, Antibody Biological and medical sciences Cell Degranulation - drug effects Dose-Response Relationship, Drug Female Fundamental and applied biological sciences. Psychology Fundamental immunology Immunobiology IMP Dehydrogenase - antagonists & inhibitors Mast Cells - drug effects Modulation of the immune response (stimulation, suppression) Mycophenolic Acid - pharmacology Peritoneal Cavity - cytology Prostaglandin D2 - analysis Rats Rats, Inbred Strains Serotonin - analysis Signal Transduction - drug effects |
| title | Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells |
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