Antiplatelet functions of a stable prostacyclin analog, SM-10906 are exerted by its inhibitory effect on inositol 1,4,5-trisphosphate production and cytosolic Ca ++ increase in rat platelets stimulated by thrombin
The mechanism of the antiplatelet functions of SM-10906, the active form of the 3-oxa-methano-prostaglandin (PG) I1 analog SM-10902, was examined in rat platelets. SM-10906 activated adenylate cyclase in crude membrane fractions, and inhibited platelet aggregation and release of adenine nucleotides...
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| Veröffentlicht in: | Thrombosis research 1995-08, Vol.79 (3), p.307-317 |
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| creator | Nishimura, Takeshi Yamamoto, Takaaki Komuro, Yoshihiro Hara, Youichi |
| description | The mechanism of the antiplatelet functions of SM-10906, the active form of the 3-oxa-methano-prostaglandin (PG) I1 analog SM-10902, was examined in rat platelets. SM-10906 activated adenylate cyclase in crude membrane fractions, and inhibited platelet aggregation and release of adenine nucleotides stimulated by thrombin. SM-10906 also inhibited malondialdehyde production induced by thrombin, but not that induced by arachidonic acid. This may account for its inhibitory effects on phospholipase A2. SM-10906 prevented thrombin-induced inositol 1,4,5-trisphosphate production, Ca
++ mobilization from intracellular Ca storage and
45Ca
++ influx into platelets, which were all reversed by pretreatment with the adenylate cyclase inhibitor 2′,5′-dideoxyadenosine. PGI2 and PGE1 have the same antiplatelet profiles in the order of PGI2 ≧ SM-10906 > PGE1. These results indicate that SM-10906 as well as PGI2 and PGE1 may exert antiplatelet activities by stimulating adenylate cyclase to prevent thrombin-induced phospholipase C and A2 activations and increase in cytosolic Ca
++ level. |
| doi_str_mv | 10.1016/0049-3848(95)00117-A |
| format | Article |
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++ mobilization from intracellular Ca storage and
45Ca
++ influx into platelets, which were all reversed by pretreatment with the adenylate cyclase inhibitor 2′,5′-dideoxyadenosine. PGI2 and PGE1 have the same antiplatelet profiles in the order of PGI2 ≧ SM-10906 > PGE1. These results indicate that SM-10906 as well as PGI2 and PGE1 may exert antiplatelet activities by stimulating adenylate cyclase to prevent thrombin-induced phospholipase C and A2 activations and increase in cytosolic Ca
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++ mobilization from intracellular Ca storage and
45Ca
++ influx into platelets, which were all reversed by pretreatment with the adenylate cyclase inhibitor 2′,5′-dideoxyadenosine. PGI2 and PGE1 have the same antiplatelet profiles in the order of PGI2 ≧ SM-10906 > PGE1. These results indicate that SM-10906 as well as PGI2 and PGE1 may exert antiplatelet activities by stimulating adenylate cyclase to prevent thrombin-induced phospholipase C and A2 activations and increase in cytosolic Ca
++ level.</description><subject>Adenylyl Cyclases - metabolism</subject><subject>Alprostadil - pharmacology</subject><subject>Animals</subject><subject>antiplatelet functions</subject><subject>Biological and medical sciences</subject><subject>Blood Platelets - drug effects</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Ca ++ influx</subject><subject>Ca ++ mobilization</subject><subject>Calcium - antagonists & inhibitors</subject><subject>Calcium - metabolism</subject><subject>Enzyme Activation</subject><subject>Epoprostenol - analogs & derivatives</subject><subject>Epoprostenol - pharmacology</subject><subject>Inositol 1,4,5-Trisphosphate - antagonists & inhibitors</subject><subject>Inositol 1,4,5-Trisphosphate - metabolism</subject><subject>IP3</subject><subject>Male</subject><subject>Medical sciences</subject><subject>PGI1 analog</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelet Activation - drug effects</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>SM-10906</subject><subject>Structure-Activity Relationship</subject><subject>Thrombin - pharmacology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcuO0zAUjRBoKAN_AJIXCIGmATuxE3uDVFW8pEEsgLXlONfUyLU7toPIh_I_OG3pkoXl-zj3nqN7quopwa8JJt0bjKmoW075S8FeYUxIX2_uVSvCe1E3tG_uV6sL5GH1KKWfBdQTwa6qK87aljTdqvqz8dkenMrgICMzeZ1t8AkFgxRKWQ0O0CGGEulZO-uR8sqFH2v09XNNsMAdUhEQ_IaYYUTDjGxOyPqdHWwOcUZgDOiMgi_FkErNIbKma1bnaNNhF8or3AvFOB2pC8GI9JxDCs5qtFXo5qbM6ggqQQlQVBn9E5yKRLufluxInncx7AfrH1cPjHIJnpz_6-r7-3ffth_r2y8fPm03t7WmrMm1aDiGvlGUCmUM6YBTNQyMQkuGTrSgWU9hBNIAZkyPrTFi5JwzMxrCyIDb6-rFaW_RfzdBynJvkwbnlIcwJdn3PW-5aAuQnoC63DJFMPIQ7V7FWRIsFzflYpVcrJKCyaObclPGnp33T8MexsvQ2b7Sf37uq6SVM1F5bdMF1nZlj2AF9vYEg3KLXxaiTNqC1zDaWNyRY7D_1_EX7by_Nw</recordid><startdate>19950801</startdate><enddate>19950801</enddate><creator>Nishimura, Takeshi</creator><creator>Yamamoto, Takaaki</creator><creator>Komuro, Yoshihiro</creator><creator>Hara, Youichi</creator><general>Elsevier Ltd</general><general>Elsevier Science</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>7X8</scope></search><sort><creationdate>19950801</creationdate><title>Antiplatelet functions of a stable prostacyclin analog, SM-10906 are exerted by its inhibitory effect on inositol 1,4,5-trisphosphate production and cytosolic Ca ++ increase in rat platelets stimulated by thrombin</title><author>Nishimura, Takeshi ; Yamamoto, Takaaki ; Komuro, Yoshihiro ; Hara, Youichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-9280e72a449aff16e84abb54e31b693ec574ede12e055cd3ff9d8885fdf151b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Adenylyl Cyclases - metabolism</topic><topic>Alprostadil - pharmacology</topic><topic>Animals</topic><topic>antiplatelet functions</topic><topic>Biological and medical sciences</topic><topic>Blood Platelets - drug effects</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Ca ++ influx</topic><topic>Ca ++ mobilization</topic><topic>Calcium - antagonists & inhibitors</topic><topic>Calcium - metabolism</topic><topic>Enzyme Activation</topic><topic>Epoprostenol - analogs & derivatives</topic><topic>Epoprostenol - pharmacology</topic><topic>Inositol 1,4,5-Trisphosphate - antagonists & inhibitors</topic><topic>Inositol 1,4,5-Trisphosphate - metabolism</topic><topic>IP3</topic><topic>Male</topic><topic>Medical sciences</topic><topic>PGI1 analog</topic><topic>Pharmacology. Drug treatments</topic><topic>Platelet Activation - drug effects</topic><topic>Platelet Aggregation Inhibitors - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>SM-10906</topic><topic>Structure-Activity Relationship</topic><topic>Thrombin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishimura, Takeshi</creatorcontrib><creatorcontrib>Yamamoto, Takaaki</creatorcontrib><creatorcontrib>Komuro, Yoshihiro</creatorcontrib><creatorcontrib>Hara, Youichi</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>MEDLINE - Academic</collection><jtitle>Thrombosis research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishimura, Takeshi</au><au>Yamamoto, Takaaki</au><au>Komuro, Yoshihiro</au><au>Hara, Youichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiplatelet functions of a stable prostacyclin analog, SM-10906 are exerted by its inhibitory effect on inositol 1,4,5-trisphosphate production and cytosolic Ca ++ increase in rat platelets stimulated by thrombin</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>1995-08-01</date><risdate>1995</risdate><volume>79</volume><issue>3</issue><spage>307</spage><epage>317</epage><pages>307-317</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><coden>THBRAA</coden><abstract>The mechanism of the antiplatelet functions of SM-10906, the active form of the 3-oxa-methano-prostaglandin (PG) I1 analog SM-10902, was examined in rat platelets. SM-10906 activated adenylate cyclase in crude membrane fractions, and inhibited platelet aggregation and release of adenine nucleotides stimulated by thrombin. SM-10906 also inhibited malondialdehyde production induced by thrombin, but not that induced by arachidonic acid. This may account for its inhibitory effects on phospholipase A2. SM-10906 prevented thrombin-induced inositol 1,4,5-trisphosphate production, Ca
++ mobilization from intracellular Ca storage and
45Ca
++ influx into platelets, which were all reversed by pretreatment with the adenylate cyclase inhibitor 2′,5′-dideoxyadenosine. PGI2 and PGE1 have the same antiplatelet profiles in the order of PGI2 ≧ SM-10906 > PGE1. These results indicate that SM-10906 as well as PGI2 and PGE1 may exert antiplatelet activities by stimulating adenylate cyclase to prevent thrombin-induced phospholipase C and A2 activations and increase in cytosolic Ca
++ level.</abstract><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>8533126</pmid><doi>10.1016/0049-3848(95)00117-A</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Thrombosis research, 1995-08, Vol.79 (3), p.307-317 |
| issn | 0049-3848 1879-2472 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adenylyl Cyclases - metabolism Alprostadil - pharmacology Animals antiplatelet functions Biological and medical sciences Blood Platelets - drug effects Blood. Blood coagulation. Reticuloendothelial system Ca ++ influx Ca ++ mobilization Calcium - antagonists & inhibitors Calcium - metabolism Enzyme Activation Epoprostenol - analogs & derivatives Epoprostenol - pharmacology Inositol 1,4,5-Trisphosphate - antagonists & inhibitors Inositol 1,4,5-Trisphosphate - metabolism IP3 Male Medical sciences PGI1 analog Pharmacology. Drug treatments Platelet Activation - drug effects Platelet Aggregation Inhibitors - pharmacology Rats Rats, Wistar SM-10906 Structure-Activity Relationship Thrombin - pharmacology |
| title | Antiplatelet functions of a stable prostacyclin analog, SM-10906 are exerted by its inhibitory effect on inositol 1,4,5-trisphosphate production and cytosolic Ca ++ increase in rat platelets stimulated by thrombin |
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