Beta-adrenergic stimulation of adenine nucleotide catabolism and purine release in human adipocytes
The effects of beta-adrenergic agonists on ATP utilization and adenine nucleotide breakdown in human adipocytes were examined. The catecholamine-induced increase in cAMP was associated with an enhancement of adenine nucleotide catabolism resulting in an increase in release of inosine and hypoxanthin...
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| Veröffentlicht in: | The Journal of clinical investigation 1990, Vol.85 (1), p.106-114 |
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| description | The effects of beta-adrenergic agonists on ATP utilization and adenine nucleotide breakdown in human adipocytes were examined. The catecholamine-induced increase in cAMP was associated with an enhancement of adenine nucleotide catabolism resulting in an increase in release of inosine and hypoxanthine which can not be reutilized for adenine nucleotide synthesis. Therefore, one-third of total cellular adenine nucleotides were irreversibly lost in the presence of 1 mumol/liter isoproterenol. The catecholamine-induced increase in purine release could be blocked by phosphodiesterase inhibitors, suggesting that cAMP is the main precursor of purines in the presence of beta-adrenergic agonists. However, epinephrine (in the simultaneous presence of the alpha 2-adrenergic blocking agent, yohimbine) and isoproterenol were 10 times more potent in stimulating purine release than in elevating cAMP. In addition, purine release ceased when cAMP was still markedly increased, suggesting a compartmentation of the cyclic nucleotide and/or involvement of the hormone-sensitive, low Km cAMP phosphodiesterase. The results document that white fat cells have an enormous potential for dissipating energy, and demonstrate that the pathway involving cAMP formation and hydrolysis constitutes the principle route of adenine nucleotide catabolism in the presence of beta-adrenergic agonists. |
| doi_str_mv | 10.1172/jci114399 |
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The catecholamine-induced increase in cAMP was associated with an enhancement of adenine nucleotide catabolism resulting in an increase in release of inosine and hypoxanthine which can not be reutilized for adenine nucleotide synthesis. Therefore, one-third of total cellular adenine nucleotides were irreversibly lost in the presence of 1 mumol/liter isoproterenol. The catecholamine-induced increase in purine release could be blocked by phosphodiesterase inhibitors, suggesting that cAMP is the main precursor of purines in the presence of beta-adrenergic agonists. However, epinephrine (in the simultaneous presence of the alpha 2-adrenergic blocking agent, yohimbine) and isoproterenol were 10 times more potent in stimulating purine release than in elevating cAMP. In addition, purine release ceased when cAMP was still markedly increased, suggesting a compartmentation of the cyclic nucleotide and/or involvement of the hormone-sensitive, low Km cAMP phosphodiesterase. The results document that white fat cells have an enormous potential for dissipating energy, and demonstrate that the pathway involving cAMP formation and hydrolysis constitutes the principle route of adenine nucleotide catabolism in the presence of beta-adrenergic agonists.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci114399</identifier><identifier>PMID: 1688563</identifier><identifier>CODEN: JCINAO</identifier><language>eng</language><publisher>Ann Arbor, MI: American Society for Clinical Investigation</publisher><subject>1-Methyl-3-isobutylxanthine - pharmacology ; 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology ; adenine nucleotides ; Adenine Nucleotides - metabolism ; Adenosine - pharmacology ; Adenosine Triphosphate - metabolism ; adipocytes ; Adipose Tissue - drug effects ; Adipose Tissue - metabolism ; Biological and medical sciences ; Cell metabolism, cell oxidation ; Cell physiology ; Cells, Cultured ; Cyclic AMP - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Hypoxanthine ; Hypoxanthines - pharmacology ; Inosine - pharmacology ; Isoproterenol - pharmacology ; Kinetics ; Lipolysis - drug effects ; Molecular and cellular biology ; Propranolol - pharmacology ; Receptors, Adrenergic, beta - drug effects ; Receptors, Adrenergic, beta - physiology</subject><ispartof>The Journal of clinical investigation, 1990, Vol.85 (1), p.106-114</ispartof><rights>1990 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-ce75acd45269925ccf00400761fda65fd8d38a8dab20870c5bb18056a92115b73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC296393/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC296393/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,4010,27904,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6937054$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1688563$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KATHER, H</creatorcontrib><title>Beta-adrenergic stimulation of adenine nucleotide catabolism and purine release in human adipocytes</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>The effects of beta-adrenergic agonists on ATP utilization and adenine nucleotide breakdown in human adipocytes were examined. The catecholamine-induced increase in cAMP was associated with an enhancement of adenine nucleotide catabolism resulting in an increase in release of inosine and hypoxanthine which can not be reutilized for adenine nucleotide synthesis. Therefore, one-third of total cellular adenine nucleotides were irreversibly lost in the presence of 1 mumol/liter isoproterenol. The catecholamine-induced increase in purine release could be blocked by phosphodiesterase inhibitors, suggesting that cAMP is the main precursor of purines in the presence of beta-adrenergic agonists. However, epinephrine (in the simultaneous presence of the alpha 2-adrenergic blocking agent, yohimbine) and isoproterenol were 10 times more potent in stimulating purine release than in elevating cAMP. In addition, purine release ceased when cAMP was still markedly increased, suggesting a compartmentation of the cyclic nucleotide and/or involvement of the hormone-sensitive, low Km cAMP phosphodiesterase. The results document that white fat cells have an enormous potential for dissipating energy, and demonstrate that the pathway involving cAMP formation and hydrolysis constitutes the principle route of adenine nucleotide catabolism in the presence of beta-adrenergic agonists.</description><subject>1-Methyl-3-isobutylxanthine - pharmacology</subject><subject>4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology</subject><subject>adenine nucleotides</subject><subject>Adenine Nucleotides - metabolism</subject><subject>Adenosine - pharmacology</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>adipocytes</subject><subject>Adipose Tissue - drug effects</subject><subject>Adipose Tissue - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell metabolism, cell oxidation</subject><subject>Cell physiology</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Hypoxanthine</subject><subject>Hypoxanthines - pharmacology</subject><subject>Inosine - pharmacology</subject><subject>Isoproterenol - pharmacology</subject><subject>Kinetics</subject><subject>Lipolysis - drug effects</subject><subject>Molecular and cellular biology</subject><subject>Propranolol - pharmacology</subject><subject>Receptors, Adrenergic, beta - drug effects</subject><subject>Receptors, Adrenergic, beta - physiology</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuLFDEUhYMoYzu68AcIWYjgojSpvBcutPExMuBG18Wt5NZMhlTSJlXC_Htr6GbUlau7ON93OXAIec7ZG85N__bGR86lcO4B2XGlbGd7YR-SHWM975wR9jF50toNY1xKJc_IGdfWKi12xH_ABToIFTPWq-hpW-K8JlhiybRMFALmmJHm1ScsSwxIPSwwlhTbTCEHeljrHVAxITSkMdPrdYa8mfFQ_O2C7Sl5NEFq-Ox0z8mPTx-_7790l98-X-zfX3ZeOrV0Ho0CH6TqtXO98n5iTDJmNJ8CaDUFG4QFG2DsmTXMq3HklikNrudcjUack3fHv4d1nDF4zEuFNBxqnKHeDgXi8G-S4_VwVX4NvdPCic1_dfJr-bliW4Y5No8pQcaytsE4JaR25r8gV9JIZvUGvj6CvpbWKk73ZTgb7pYbvu4vjstt7Iu_2_8hj1Nt-ctTDs1DmipkH9s9pp0wTEnxG8ADoqo</recordid><startdate>1990</startdate><enddate>1990</enddate><creator>KATHER, H</creator><general>American Society for Clinical Investigation</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>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>1990</creationdate><title>Beta-adrenergic stimulation of adenine nucleotide catabolism and purine release in human adipocytes</title><author>KATHER, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-ce75acd45269925ccf00400761fda65fd8d38a8dab20870c5bb18056a92115b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>1-Methyl-3-isobutylxanthine - pharmacology</topic><topic>4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology</topic><topic>adenine nucleotides</topic><topic>Adenine Nucleotides - metabolism</topic><topic>Adenosine - pharmacology</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>adipocytes</topic><topic>Adipose Tissue - drug effects</topic><topic>Adipose Tissue - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell metabolism, cell oxidation</topic><topic>Cell physiology</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Hypoxanthine</topic><topic>Hypoxanthines - pharmacology</topic><topic>Inosine - pharmacology</topic><topic>Isoproterenol - pharmacology</topic><topic>Kinetics</topic><topic>Lipolysis - drug effects</topic><topic>Molecular and cellular biology</topic><topic>Propranolol - pharmacology</topic><topic>Receptors, Adrenergic, beta - drug effects</topic><topic>Receptors, Adrenergic, beta - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KATHER, H</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KATHER, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Beta-adrenergic stimulation of adenine nucleotide catabolism and purine release in human adipocytes</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>1990</date><risdate>1990</risdate><volume>85</volume><issue>1</issue><spage>106</spage><epage>114</epage><pages>106-114</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><coden>JCINAO</coden><abstract>The effects of beta-adrenergic agonists on ATP utilization and adenine nucleotide breakdown in human adipocytes were examined. The catecholamine-induced increase in cAMP was associated with an enhancement of adenine nucleotide catabolism resulting in an increase in release of inosine and hypoxanthine which can not be reutilized for adenine nucleotide synthesis. Therefore, one-third of total cellular adenine nucleotides were irreversibly lost in the presence of 1 mumol/liter isoproterenol. The catecholamine-induced increase in purine release could be blocked by phosphodiesterase inhibitors, suggesting that cAMP is the main precursor of purines in the presence of beta-adrenergic agonists. However, epinephrine (in the simultaneous presence of the alpha 2-adrenergic blocking agent, yohimbine) and isoproterenol were 10 times more potent in stimulating purine release than in elevating cAMP. In addition, purine release ceased when cAMP was still markedly increased, suggesting a compartmentation of the cyclic nucleotide and/or involvement of the hormone-sensitive, low Km cAMP phosphodiesterase. The results document that white fat cells have an enormous potential for dissipating energy, and demonstrate that the pathway involving cAMP formation and hydrolysis constitutes the principle route of adenine nucleotide catabolism in the presence of beta-adrenergic agonists.</abstract><cop>Ann Arbor, MI</cop><pub>American Society for Clinical Investigation</pub><pmid>1688563</pmid><doi>10.1172/jci114399</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | 1-Methyl-3-isobutylxanthine - pharmacology 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology adenine nucleotides Adenine Nucleotides - metabolism Adenosine - pharmacology Adenosine Triphosphate - metabolism adipocytes Adipose Tissue - drug effects Adipose Tissue - metabolism Biological and medical sciences Cell metabolism, cell oxidation Cell physiology Cells, Cultured Cyclic AMP - metabolism Female Fundamental and applied biological sciences. Psychology Humans Hypoxanthine Hypoxanthines - pharmacology Inosine - pharmacology Isoproterenol - pharmacology Kinetics Lipolysis - drug effects Molecular and cellular biology Propranolol - pharmacology Receptors, Adrenergic, beta - drug effects Receptors, Adrenergic, beta - physiology |
| title | Beta-adrenergic stimulation of adenine nucleotide catabolism and purine release in human adipocytes |
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