Loading…
Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272
By the formation of cGMP, nitric oxide (NO)-sensitive guanylyl cyclase (GC) acts as the effector for the signaling molecule NO and mediates the relaxation of vascular smooth muscle and the inhibition of platelet aggregation. The compounds YC-1 and BAY 41-2272 are regarded as NO-independent activator...
Saved in:
| Published in: | Circulation (New York, N.Y.) N.Y.), 2004-04, Vol.109 (14), p.1711-1713 |
|---|---|
| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c506t-2841e1d1e25dbdbb4d402381f753d58e0c3964dc317acf15adad3a071b62290d3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c506t-2841e1d1e25dbdbb4d402381f753d58e0c3964dc317acf15adad3a071b62290d3 |
| container_end_page | 1713 |
| container_issue | 14 |
| container_start_page | 1711 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 109 |
| creator | MULLERSHAUSEN, Florian RUSSWURM, Michael FRIEBE, Andreas KOESLING, Doris |
| description | By the formation of cGMP, nitric oxide (NO)-sensitive guanylyl cyclase (GC) acts as the effector for the signaling molecule NO and mediates the relaxation of vascular smooth muscle and the inhibition of platelet aggregation. The compounds YC-1 and BAY 41-2272 are regarded as NO-independent activators and sensitizers of NO-sensitive GC. In vivo effects, for example, lowering blood pressure and prolonging tail-bleeding times, turn the compounds into promising candidates for the therapy of cardiovascular diseases. However, YC-1 has also been shown to inhibit the major cGMP-degrading enzyme phosphodiesterase type 5 (PDE5). The synergistic properties of YC-1 on cGMP formation and degradation lead to an excessive NO-induced cGMP accumulation in cells, explaining the observed physiological effects. We assessed a potential inhibition of PDE5 by the new GC activator BAY 41-2272.
The effects of BAY 41-2272 on NO-sensitive GC and PDE5 activities were tested in vitro. BAY 41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. In intact platelets, BAY 41-2272 greatly potentiated the NO-induced cGMP response that was caused by a synergistic effect of BAY 41-2272 on cGMP formation and degradation.
The physiological effects of BAY 41-2272, which are commonly ascribed to the NO-independent activation of NO-sensitive GC, are rather due to the synergism of sensitization of NO-sensitive GC and inhibition of PDE5. |
| doi_str_mv | 10.1161/01.cir.0000126286.47618.bd |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71817133</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71817133</sourcerecordid><originalsourceid>FETCH-LOGICAL-c506t-2841e1d1e25dbdbb4d402381f753d58e0c3964dc317acf15adad3a071b62290d3</originalsourceid><addsrcrecordid>eNpNkG9r2zAQxsVYWdNsX2GIwfrOrk5_7b5L0rUNFAple7FXQpbkRcOxU8kJ9befsgbag-M4-N1zdw9C34CUABKuCJQ2xJLkACppJUuuJFRl4z6gGQjKCy5Y_RHNMlAXilF6ji5S-ptbyZT4hM5BEClrQWaoX_eb0IQxDD0eWrzbDCmnCz6NPprk8TjtPBa4mfC48djYMRzMOMQj3IcxBouHl-B8kXyfsszB4z9700_d1GE72e4osVz8xhwKShX9jM5a0yX_5VTn6Nftj5-r--Lh8W69WjwUNl82FrTi4MGBp8I1rmm444SyClolmBOVJ5bVkjvLQBnbgjDOOGaIgkZSWhPH5ujyVXcXh-d9fkZvQ7K-60zvh33SCipQwFgGr19BG4eUom_1LoatiZMGoo9uawJ6tX7Sb27r_27r5U0e_nrasm-23r2NnuzNwPcTYJI1XRtNb0N6x0nOhFDsHw-aiRs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71817133</pqid></control><display><type>article</type><title>Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272</title><source>EZB Electronic Journals Library</source><creator>MULLERSHAUSEN, Florian ; RUSSWURM, Michael ; FRIEBE, Andreas ; KOESLING, Doris</creator><creatorcontrib>MULLERSHAUSEN, Florian ; RUSSWURM, Michael ; FRIEBE, Andreas ; KOESLING, Doris</creatorcontrib><description>By the formation of cGMP, nitric oxide (NO)-sensitive guanylyl cyclase (GC) acts as the effector for the signaling molecule NO and mediates the relaxation of vascular smooth muscle and the inhibition of platelet aggregation. The compounds YC-1 and BAY 41-2272 are regarded as NO-independent activators and sensitizers of NO-sensitive GC. In vivo effects, for example, lowering blood pressure and prolonging tail-bleeding times, turn the compounds into promising candidates for the therapy of cardiovascular diseases. However, YC-1 has also been shown to inhibit the major cGMP-degrading enzyme phosphodiesterase type 5 (PDE5). The synergistic properties of YC-1 on cGMP formation and degradation lead to an excessive NO-induced cGMP accumulation in cells, explaining the observed physiological effects. We assessed a potential inhibition of PDE5 by the new GC activator BAY 41-2272.
The effects of BAY 41-2272 on NO-sensitive GC and PDE5 activities were tested in vitro. BAY 41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. In intact platelets, BAY 41-2272 greatly potentiated the NO-induced cGMP response that was caused by a synergistic effect of BAY 41-2272 on cGMP formation and degradation.
The physiological effects of BAY 41-2272, which are commonly ascribed to the NO-independent activation of NO-sensitive GC, are rather due to the synergism of sensitization of NO-sensitive GC and inhibition of PDE5.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.0000126286.47618.bd</identifier><identifier>PMID: 15066950</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors ; 3',5'-Cyclic-GMP Phosphodiesterases - genetics ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Line ; Cyclic GMP - physiology ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Enzyme Activation - drug effects ; Guanylate Cyclase ; Humans ; Indazoles - pharmacology ; Kidney ; Medical sciences ; Nitric Oxide - physiology ; Nitric Oxide Donors - metabolism ; Phosphodiesterase Inhibitors - pharmacology ; Pyrazoles - pharmacology ; Pyridines - pharmacology ; Quaternary Ammonium Compounds - metabolism ; Receptors, Cytoplasmic and Nuclear - physiology ; Recombinant Fusion Proteins - antagonists & inhibitors ; S-Nitrosoglutathione - pharmacology ; Soluble Guanylyl Cyclase ; Transfection ; Vasodilation - physiology</subject><ispartof>Circulation (New York, N.Y.), 2004-04, Vol.109 (14), p.1711-1713</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-2841e1d1e25dbdbb4d402381f753d58e0c3964dc317acf15adad3a071b62290d3</citedby><cites>FETCH-LOGICAL-c506t-2841e1d1e25dbdbb4d402381f753d58e0c3964dc317acf15adad3a071b62290d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15643557$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15066950$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MULLERSHAUSEN, Florian</creatorcontrib><creatorcontrib>RUSSWURM, Michael</creatorcontrib><creatorcontrib>FRIEBE, Andreas</creatorcontrib><creatorcontrib>KOESLING, Doris</creatorcontrib><title>Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>By the formation of cGMP, nitric oxide (NO)-sensitive guanylyl cyclase (GC) acts as the effector for the signaling molecule NO and mediates the relaxation of vascular smooth muscle and the inhibition of platelet aggregation. The compounds YC-1 and BAY 41-2272 are regarded as NO-independent activators and sensitizers of NO-sensitive GC. In vivo effects, for example, lowering blood pressure and prolonging tail-bleeding times, turn the compounds into promising candidates for the therapy of cardiovascular diseases. However, YC-1 has also been shown to inhibit the major cGMP-degrading enzyme phosphodiesterase type 5 (PDE5). The synergistic properties of YC-1 on cGMP formation and degradation lead to an excessive NO-induced cGMP accumulation in cells, explaining the observed physiological effects. We assessed a potential inhibition of PDE5 by the new GC activator BAY 41-2272.
The effects of BAY 41-2272 on NO-sensitive GC and PDE5 activities were tested in vitro. BAY 41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. In intact platelets, BAY 41-2272 greatly potentiated the NO-induced cGMP response that was caused by a synergistic effect of BAY 41-2272 on cGMP formation and degradation.
The physiological effects of BAY 41-2272, which are commonly ascribed to the NO-independent activation of NO-sensitive GC, are rather due to the synergism of sensitization of NO-sensitive GC and inhibition of PDE5.</description><subject>3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors</subject><subject>3',5'-Cyclic-GMP Phosphodiesterases - genetics</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cell Line</subject><subject>Cyclic GMP - physiology</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 5</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Enzyme Activation - drug effects</subject><subject>Guanylate Cyclase</subject><subject>Humans</subject><subject>Indazoles - pharmacology</subject><subject>Kidney</subject><subject>Medical sciences</subject><subject>Nitric Oxide - physiology</subject><subject>Nitric Oxide Donors - metabolism</subject><subject>Phosphodiesterase Inhibitors - pharmacology</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Quaternary Ammonium Compounds - metabolism</subject><subject>Receptors, Cytoplasmic and Nuclear - physiology</subject><subject>Recombinant Fusion Proteins - antagonists & inhibitors</subject><subject>S-Nitrosoglutathione - pharmacology</subject><subject>Soluble Guanylyl Cyclase</subject><subject>Transfection</subject><subject>Vasodilation - physiology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNpNkG9r2zAQxsVYWdNsX2GIwfrOrk5_7b5L0rUNFAple7FXQpbkRcOxU8kJ9befsgbag-M4-N1zdw9C34CUABKuCJQ2xJLkACppJUuuJFRl4z6gGQjKCy5Y_RHNMlAXilF6ji5S-ptbyZT4hM5BEClrQWaoX_eb0IQxDD0eWrzbDCmnCz6NPprk8TjtPBa4mfC48djYMRzMOMQj3IcxBouHl-B8kXyfsszB4z9700_d1GE72e4osVz8xhwKShX9jM5a0yX_5VTn6Nftj5-r--Lh8W69WjwUNl82FrTi4MGBp8I1rmm444SyClolmBOVJ5bVkjvLQBnbgjDOOGaIgkZSWhPH5ujyVXcXh-d9fkZvQ7K-60zvh33SCipQwFgGr19BG4eUom_1LoatiZMGoo9uawJ6tX7Sb27r_27r5U0e_nrasm-23r2NnuzNwPcTYJI1XRtNb0N6x0nOhFDsHw-aiRs</recordid><startdate>20040413</startdate><enddate>20040413</enddate><creator>MULLERSHAUSEN, Florian</creator><creator>RUSSWURM, Michael</creator><creator>FRIEBE, Andreas</creator><creator>KOESLING, Doris</creator><general>Lippincott Williams & Wilkins</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>20040413</creationdate><title>Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272</title><author>MULLERSHAUSEN, Florian ; RUSSWURM, Michael ; FRIEBE, Andreas ; KOESLING, Doris</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c506t-2841e1d1e25dbdbb4d402381f753d58e0c3964dc317acf15adad3a071b62290d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors</topic><topic>3',5'-Cyclic-GMP Phosphodiesterases - genetics</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cell Line</topic><topic>Cyclic GMP - physiology</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 5</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Enzyme Activation - drug effects</topic><topic>Guanylate Cyclase</topic><topic>Humans</topic><topic>Indazoles - pharmacology</topic><topic>Kidney</topic><topic>Medical sciences</topic><topic>Nitric Oxide - physiology</topic><topic>Nitric Oxide Donors - metabolism</topic><topic>Phosphodiesterase Inhibitors - pharmacology</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyridines - pharmacology</topic><topic>Quaternary Ammonium Compounds - metabolism</topic><topic>Receptors, Cytoplasmic and Nuclear - physiology</topic><topic>Recombinant Fusion Proteins - antagonists & inhibitors</topic><topic>S-Nitrosoglutathione - pharmacology</topic><topic>Soluble Guanylyl Cyclase</topic><topic>Transfection</topic><topic>Vasodilation - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MULLERSHAUSEN, Florian</creatorcontrib><creatorcontrib>RUSSWURM, Michael</creatorcontrib><creatorcontrib>FRIEBE, Andreas</creatorcontrib><creatorcontrib>KOESLING, Doris</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>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MULLERSHAUSEN, Florian</au><au>RUSSWURM, Michael</au><au>FRIEBE, Andreas</au><au>KOESLING, Doris</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2004-04-13</date><risdate>2004</risdate><volume>109</volume><issue>14</issue><spage>1711</spage><epage>1713</epage><pages>1711-1713</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>By the formation of cGMP, nitric oxide (NO)-sensitive guanylyl cyclase (GC) acts as the effector for the signaling molecule NO and mediates the relaxation of vascular smooth muscle and the inhibition of platelet aggregation. The compounds YC-1 and BAY 41-2272 are regarded as NO-independent activators and sensitizers of NO-sensitive GC. In vivo effects, for example, lowering blood pressure and prolonging tail-bleeding times, turn the compounds into promising candidates for the therapy of cardiovascular diseases. However, YC-1 has also been shown to inhibit the major cGMP-degrading enzyme phosphodiesterase type 5 (PDE5). The synergistic properties of YC-1 on cGMP formation and degradation lead to an excessive NO-induced cGMP accumulation in cells, explaining the observed physiological effects. We assessed a potential inhibition of PDE5 by the new GC activator BAY 41-2272.
The effects of BAY 41-2272 on NO-sensitive GC and PDE5 activities were tested in vitro. BAY 41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. In intact platelets, BAY 41-2272 greatly potentiated the NO-induced cGMP response that was caused by a synergistic effect of BAY 41-2272 on cGMP formation and degradation.
The physiological effects of BAY 41-2272, which are commonly ascribed to the NO-independent activation of NO-sensitive GC, are rather due to the synergism of sensitization of NO-sensitive GC and inhibition of PDE5.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>15066950</pmid><doi>10.1161/01.cir.0000126286.47618.bd</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2004-04, Vol.109 (14), p.1711-1713 |
| issn | 0009-7322 1524-4539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71817133 |
| source | EZB Electronic Journals Library |
| subjects | 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors 3',5'-Cyclic-GMP Phosphodiesterases - genetics Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Line Cyclic GMP - physiology Cyclic Nucleotide Phosphodiesterases, Type 5 Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Enzyme Activation - drug effects Guanylate Cyclase Humans Indazoles - pharmacology Kidney Medical sciences Nitric Oxide - physiology Nitric Oxide Donors - metabolism Phosphodiesterase Inhibitors - pharmacology Pyrazoles - pharmacology Pyridines - pharmacology Quaternary Ammonium Compounds - metabolism Receptors, Cytoplasmic and Nuclear - physiology Recombinant Fusion Proteins - antagonists & inhibitors S-Nitrosoglutathione - pharmacology Soluble Guanylyl Cyclase Transfection Vasodilation - physiology |
| title | Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272 |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T23%3A08%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20phosphodiesterase%20type%205%20by%20the%20activator%20of%20nitric%20oxide-sensitive%20guanylyl%20cyclase%20BAY%2041-2272&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=MULLERSHAUSEN,%20Florian&rft.date=2004-04-13&rft.volume=109&rft.issue=14&rft.spage=1711&rft.epage=1713&rft.pages=1711-1713&rft.issn=0009-7322&rft.eissn=1524-4539&rft.coden=CIRCAZ&rft_id=info:doi/10.1161/01.cir.0000126286.47618.bd&rft_dat=%3Cproquest_cross%3E71817133%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c506t-2841e1d1e25dbdbb4d402381f753d58e0c3964dc317acf15adad3a071b62290d3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=71817133&rft_id=info:pmid/15066950&rfr_iscdi=true |