Inhibition of type 1 protein phosphatase activity by activation of β-adrenoceptors in ventricular myocardium
The regulation of protein phosphatase (PP) activity by cardiac β-adrenergic receptor stimulation with isoproterenol (ISO) was studied in four groups of guinea pigs consisting of seven animals each. Group 1 received the vehicle solution only intraperitoneally; group 2, 6 μg/kg of ISO; group 3, 60 μg/...
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| Veröffentlicht in: | Biochemical pharmacology 2002-03, Vol.63 (6), p.1069-1076 |
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| creator | Gupta, Ramesh C Neumann, John Watanabe, August M Sabbah, Hani N |
| description | The regulation of protein phosphatase (PP) activity by cardiac β-adrenergic receptor stimulation with isoproterenol (ISO) was studied in four groups of guinea pigs consisting of seven animals each. Group 1 received the vehicle solution only intraperitoneally; group 2, 6
μg/kg of ISO; group 3, 60
μg/kg of ISO; and group 4, 600
μg/kg of ISO. Total PP activity (consisting of both type 1 and type 2A PP), activity of each PP subtype, the cAMP-dependent protein kinase activity ratio (−cAMP/+cAMP), the phosphorylation of PP inhibitor 1, and the phosphorylation of phospholamban were measured in ventricular tissue. PP activity was also studied in ventricular cardiomyocytes isolated from guinea pigs treated with and without 1
μM ISO or 1
μM ISO plus 10
μM propranolol, an antagonist of the β-adrenoceptor. PP activity decreased significantly in membrane vesicles, but not in cytosolic fractions, of guinea pigs treated with 60 and 600
μg/kg of ISO compared with untreated animals. The PKA activity ratio, PLB phosphorylation, and PP inhibitor 1 phosphorylation increased in ventricles of guinea pigs treated with 60 and 600
μg/kg of ISO compared with vehicle-treated animals. The decrease in overall PP activity was due primarily to a reduction in type 1 but not type 2A PP activity. In isolated ventricular cardiomyocytes, PP activity was decreased significantly after treatment with 1
μM ISO, and this inhibition was reversed by treatment with 10
μM propranolol. The membrane vesicles of group 1 animals did not release any catalytic subunit of type 1 PP upon phosphorylation by exogenous PKA. These results indicate that activation of cardiac β-adrenoceptors inhibits type 1 PP activity
via phosphorylation of PP inhibitor 1 in the ventricles. This effect is associated with the well-known effect of ISO on increases in the PKA activity ratio and PLB phosphorylation. Inhibition of type 1 PP activity could be one possible mechanism, in addition to activation of adenylate cyclase, by which ISO mediates enhanced contractility of the heart. |
| doi_str_mv | 10.1016/S0006-2952(02)00851-1 |
| format | Article |
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μg/kg of ISO; group 3, 60
μg/kg of ISO; and group 4, 600
μg/kg of ISO. Total PP activity (consisting of both type 1 and type 2A PP), activity of each PP subtype, the cAMP-dependent protein kinase activity ratio (−cAMP/+cAMP), the phosphorylation of PP inhibitor 1, and the phosphorylation of phospholamban were measured in ventricular tissue. PP activity was also studied in ventricular cardiomyocytes isolated from guinea pigs treated with and without 1
μM ISO or 1
μM ISO plus 10
μM propranolol, an antagonist of the β-adrenoceptor. PP activity decreased significantly in membrane vesicles, but not in cytosolic fractions, of guinea pigs treated with 60 and 600
μg/kg of ISO compared with untreated animals. The PKA activity ratio, PLB phosphorylation, and PP inhibitor 1 phosphorylation increased in ventricles of guinea pigs treated with 60 and 600
μg/kg of ISO compared with vehicle-treated animals. The decrease in overall PP activity was due primarily to a reduction in type 1 but not type 2A PP activity. In isolated ventricular cardiomyocytes, PP activity was decreased significantly after treatment with 1
μM ISO, and this inhibition was reversed by treatment with 10
μM propranolol. The membrane vesicles of group 1 animals did not release any catalytic subunit of type 1 PP upon phosphorylation by exogenous PKA. These results indicate that activation of cardiac β-adrenoceptors inhibits type 1 PP activity
via phosphorylation of PP inhibitor 1 in the ventricles. This effect is associated with the well-known effect of ISO on increases in the PKA activity ratio and PLB phosphorylation. Inhibition of type 1 PP activity could be one possible mechanism, in addition to activation of adenylate cyclase, by which ISO mediates enhanced contractility of the heart.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/S0006-2952(02)00851-1</identifier><identifier>PMID: 11931839</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adrenergic beta-Agonists - pharmacology ; Animals ; Biological and medical sciences ; Calcium-Binding Proteins - metabolism ; Carrier Proteins ; Catecholaminergic system ; Cyclic AMP - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Enzyme Inhibitors - pharmacology ; Female ; Guinea Pigs ; Heart Ventricles - cytology ; Heart Ventricles - enzymology ; Heart Ventricles - metabolism ; In Vitro Techniques ; Inhibitor 1 ; Intracellular Signaling Peptides and Proteins ; Isoproterenol ; Isoproterenol - pharmacology ; Male ; Medical sciences ; Myocardium - enzymology ; Myocardium - metabolism ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Phospholamban ; Phosphoprotein Phosphatases - antagonists & inhibitors ; Phosphoprotein Phosphatases - metabolism ; Phosphorylation ; Protein phosphatase ; Proteins - pharmacology ; Receptors, Adrenergic, beta - metabolism ; RNA-Binding Proteins - metabolism ; Ventricles</subject><ispartof>Biochemical pharmacology, 2002-03, Vol.63 (6), p.1069-1076</ispartof><rights>2002 Elsevier Science Inc.</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-65a0026c9f6715d1d47c424107bb2b2859258d0b4800eb6b09da5a3eadb47e353</citedby><cites>FETCH-LOGICAL-c391t-65a0026c9f6715d1d47c424107bb2b2859258d0b4800eb6b09da5a3eadb47e353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-2952(02)00851-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13705513$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11931839$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gupta, Ramesh C</creatorcontrib><creatorcontrib>Neumann, John</creatorcontrib><creatorcontrib>Watanabe, August M</creatorcontrib><creatorcontrib>Sabbah, Hani N</creatorcontrib><title>Inhibition of type 1 protein phosphatase activity by activation of β-adrenoceptors in ventricular myocardium</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>The regulation of protein phosphatase (PP) activity by cardiac β-adrenergic receptor stimulation with isoproterenol (ISO) was studied in four groups of guinea pigs consisting of seven animals each. Group 1 received the vehicle solution only intraperitoneally; group 2, 6
μg/kg of ISO; group 3, 60
μg/kg of ISO; and group 4, 600
μg/kg of ISO. Total PP activity (consisting of both type 1 and type 2A PP), activity of each PP subtype, the cAMP-dependent protein kinase activity ratio (−cAMP/+cAMP), the phosphorylation of PP inhibitor 1, and the phosphorylation of phospholamban were measured in ventricular tissue. PP activity was also studied in ventricular cardiomyocytes isolated from guinea pigs treated with and without 1
μM ISO or 1
μM ISO plus 10
μM propranolol, an antagonist of the β-adrenoceptor. PP activity decreased significantly in membrane vesicles, but not in cytosolic fractions, of guinea pigs treated with 60 and 600
μg/kg of ISO compared with untreated animals. The PKA activity ratio, PLB phosphorylation, and PP inhibitor 1 phosphorylation increased in ventricles of guinea pigs treated with 60 and 600
μg/kg of ISO compared with vehicle-treated animals. The decrease in overall PP activity was due primarily to a reduction in type 1 but not type 2A PP activity. In isolated ventricular cardiomyocytes, PP activity was decreased significantly after treatment with 1
μM ISO, and this inhibition was reversed by treatment with 10
μM propranolol. The membrane vesicles of group 1 animals did not release any catalytic subunit of type 1 PP upon phosphorylation by exogenous PKA. These results indicate that activation of cardiac β-adrenoceptors inhibits type 1 PP activity
via phosphorylation of PP inhibitor 1 in the ventricles. This effect is associated with the well-known effect of ISO on increases in the PKA activity ratio and PLB phosphorylation. Inhibition of type 1 PP activity could be one possible mechanism, in addition to activation of adenylate cyclase, by which ISO mediates enhanced contractility of the heart.</description><subject>Adrenergic beta-Agonists - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Carrier Proteins</subject><subject>Catecholaminergic system</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Guinea Pigs</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - enzymology</subject><subject>Heart Ventricles - metabolism</subject><subject>In Vitro Techniques</subject><subject>Inhibitor 1</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Isoproterenol</subject><subject>Isoproterenol - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Myocardium - enzymology</subject><subject>Myocardium - metabolism</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Phospholamban</subject><subject>Phosphoprotein Phosphatases - antagonists & inhibitors</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Phosphorylation</subject><subject>Protein phosphatase</subject><subject>Proteins - pharmacology</subject><subject>Receptors, Adrenergic, beta - metabolism</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Ventricles</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtu1TAQhi0EoqeFRwB5QwWLFE8c57JCqKJQqVIXwNryZaJjlMTBdo6U1-JBeKY6nANdIo3ksfX9Y_sj5BWwK2BQv__KGKuLshPlW1a-Y6wVUMATsoO24fm4bp-S3T_kjJzH-GPbtjU8J2cAHYeWdzsy3k57p11yfqK-p2mdkQKdg0_oJjrvfZz3KqmIVJnkDi6tVK_HXv0N_f5VKBtw8gbn5EOkOXnAKQVnlkEFOq7eqGDdMr4gz3o1RHx5Wi_I95tP366_FHf3n2-vP94VhneQilooxsradH3dgLBgq8ZUZQWs0brUZSu6UrSW6aplDHWtWWeVUByV1VWDXPALcnmcmz_yc8GY5OiiwWFQE_olyjy1KQE2UBxBE3yMAXs5BzeqsEpgcvMs_3iWm0TJcm2eJeTc69MFix7RPqZOYjPw5gSoaNTQBzUZFx853jAhgGfuw5HDrOPgMMhoHE4GrQtokrTe_ecpD-oum9c</recordid><startdate>20020315</startdate><enddate>20020315</enddate><creator>Gupta, Ramesh C</creator><creator>Neumann, John</creator><creator>Watanabe, August M</creator><creator>Sabbah, Hani N</creator><general>Elsevier Inc</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>20020315</creationdate><title>Inhibition of type 1 protein phosphatase activity by activation of β-adrenoceptors in ventricular myocardium</title><author>Gupta, Ramesh C ; Neumann, John ; Watanabe, August M ; Sabbah, Hani N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-65a0026c9f6715d1d47c424107bb2b2859258d0b4800eb6b09da5a3eadb47e353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adrenergic beta-Agonists - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Carrier Proteins</topic><topic>Catecholaminergic system</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Guinea Pigs</topic><topic>Heart Ventricles - cytology</topic><topic>Heart Ventricles - enzymology</topic><topic>Heart Ventricles - metabolism</topic><topic>In Vitro Techniques</topic><topic>Inhibitor 1</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Isoproterenol</topic><topic>Isoproterenol - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Myocardium - enzymology</topic><topic>Myocardium - metabolism</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Phospholamban</topic><topic>Phosphoprotein Phosphatases - antagonists & inhibitors</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Phosphorylation</topic><topic>Protein phosphatase</topic><topic>Proteins - pharmacology</topic><topic>Receptors, Adrenergic, beta - metabolism</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Ventricles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gupta, Ramesh C</creatorcontrib><creatorcontrib>Neumann, John</creatorcontrib><creatorcontrib>Watanabe, August M</creatorcontrib><creatorcontrib>Sabbah, Hani N</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>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gupta, Ramesh C</au><au>Neumann, John</au><au>Watanabe, August M</au><au>Sabbah, Hani N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of type 1 protein phosphatase activity by activation of β-adrenoceptors in ventricular myocardium</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2002-03-15</date><risdate>2002</risdate><volume>63</volume><issue>6</issue><spage>1069</spage><epage>1076</epage><pages>1069-1076</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>The regulation of protein phosphatase (PP) activity by cardiac β-adrenergic receptor stimulation with isoproterenol (ISO) was studied in four groups of guinea pigs consisting of seven animals each. Group 1 received the vehicle solution only intraperitoneally; group 2, 6
μg/kg of ISO; group 3, 60
μg/kg of ISO; and group 4, 600
μg/kg of ISO. Total PP activity (consisting of both type 1 and type 2A PP), activity of each PP subtype, the cAMP-dependent protein kinase activity ratio (−cAMP/+cAMP), the phosphorylation of PP inhibitor 1, and the phosphorylation of phospholamban were measured in ventricular tissue. PP activity was also studied in ventricular cardiomyocytes isolated from guinea pigs treated with and without 1
μM ISO or 1
μM ISO plus 10
μM propranolol, an antagonist of the β-adrenoceptor. PP activity decreased significantly in membrane vesicles, but not in cytosolic fractions, of guinea pigs treated with 60 and 600
μg/kg of ISO compared with untreated animals. The PKA activity ratio, PLB phosphorylation, and PP inhibitor 1 phosphorylation increased in ventricles of guinea pigs treated with 60 and 600
μg/kg of ISO compared with vehicle-treated animals. The decrease in overall PP activity was due primarily to a reduction in type 1 but not type 2A PP activity. In isolated ventricular cardiomyocytes, PP activity was decreased significantly after treatment with 1
μM ISO, and this inhibition was reversed by treatment with 10
μM propranolol. The membrane vesicles of group 1 animals did not release any catalytic subunit of type 1 PP upon phosphorylation by exogenous PKA. These results indicate that activation of cardiac β-adrenoceptors inhibits type 1 PP activity
via phosphorylation of PP inhibitor 1 in the ventricles. This effect is associated with the well-known effect of ISO on increases in the PKA activity ratio and PLB phosphorylation. Inhibition of type 1 PP activity could be one possible mechanism, in addition to activation of adenylate cyclase, by which ISO mediates enhanced contractility of the heart.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11931839</pmid><doi>10.1016/S0006-2952(02)00851-1</doi><tpages>8</tpages></addata></record> |
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| subjects | Adrenergic beta-Agonists - pharmacology Animals Biological and medical sciences Calcium-Binding Proteins - metabolism Carrier Proteins Catecholaminergic system Cyclic AMP - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Enzyme Inhibitors - pharmacology Female Guinea Pigs Heart Ventricles - cytology Heart Ventricles - enzymology Heart Ventricles - metabolism In Vitro Techniques Inhibitor 1 Intracellular Signaling Peptides and Proteins Isoproterenol Isoproterenol - pharmacology Male Medical sciences Myocardium - enzymology Myocardium - metabolism Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Phospholamban Phosphoprotein Phosphatases - antagonists & inhibitors Phosphoprotein Phosphatases - metabolism Phosphorylation Protein phosphatase Proteins - pharmacology Receptors, Adrenergic, beta - metabolism RNA-Binding Proteins - metabolism Ventricles |
| title | Inhibition of type 1 protein phosphatase activity by activation of β-adrenoceptors in ventricular myocardium |
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