Eintrag weiter verarbeiten
Lidocaine Enhances GαiProtein Function
Gespeichert in:
| Zeitschriftentitel: | Anesthesiology |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Anesthesiology, 99, 2003, 5, S. 1093-1101 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
| Schlagwörter: |
| author_facet |
Benkwitz, Claudia Garrison, James C. Linden, Joel Durieux, Marcel E. Hollmann, Markus W. Benkwitz, Claudia Garrison, James C. Linden, Joel Durieux, Marcel E. Hollmann, Markus W. |
|---|---|
| author |
Benkwitz, Claudia Garrison, James C. Linden, Joel Durieux, Marcel E. Hollmann, Markus W. |
| spellingShingle |
Benkwitz, Claudia Garrison, James C. Linden, Joel Durieux, Marcel E. Hollmann, Markus W. Anesthesiology Lidocaine Enhances GαiProtein Function Anesthesiology and Pain Medicine |
| author_sort |
benkwitz, claudia |
| spelling |
Benkwitz, Claudia Garrison, James C. Linden, Joel Durieux, Marcel E. Hollmann, Markus W. 0003-3022 Ovid Technologies (Wolters Kluwer Health) Anesthesiology and Pain Medicine http://dx.doi.org/10.1097/00000542-200311000-00015 <jats:sec> <jats:title>Background</jats:title> <jats:p>Local anesthetics inhibit several G protein-coupled receptors by interaction with the Galphaq protein subunit. It is not known whether this effect on G protein function can be extrapolated to other classes of G proteins. The authors investigated interactions of lidocaine with the human adenosine 1 receptor (hA1R)-coupled signaling pathway. Activated A1Rs couple to adenylate cyclase via the pertussis toxin sensitive Galphai protein, thereby decreasing cyclic adenosine monophosphate formation. A1Rs are widely expressed and abundant in the spinal cord, brain, and heart. Interactions of LAs with the hA1R-coupled transduction cascade therefore might produce a broad range of clinically relevant effects.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The function of hA1Rs stably expressed in Chinese hamster ovary cells was determined with assays of cyclic adenosine monophosphate, receptor binding, and guanosine diphosphate/guanosine triphosphate gamma35S exchange by using reconstituted defined G protein subunits. Involvement of phosphodiesterase and Galphai was characterized by using the phosphodiesterase inhibitor rolipram and pertussis toxin, respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Lidocaine (10-9-10-1 M) had no significant effects on agonist or antagonist binding to the hA1R or on receptor-G protein interactions. However, cyclic adenosine monophosphate levels were reduced significantly to 50% by the LAs, even in the absence of an A1R agonist or presence of an A1R antagonist. This effect was unaffected by rolipram (10 mum), but abolished completely by pretreatment with pertussis toxin, which inactivates the Galphai protein. Therefore, the main target site for LAs in this pathway is located upstream from adenylate cyclase.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Lidocaine potentiates Galphai-coupled A1R signaling by reducing cyclic adenosine monophosphate production. The study suggests an interaction site for LAs in a Galphai-coupled signaling pathway, with the Galphai protein representing the prime candidate. Taken together with previous results showing inhibitory LA interactions on the Galphaq protein subunit, the data in the current study support the hypothesis that specific G protein subunits represent alternative sites of LA action.</jats:p> </jats:sec> Lidocaine Enhances GαiProtein Function Anesthesiology |
| doi_str_mv |
10.1097/00000542-200311000-00015 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA5Ny8wMDAwMDU0Mi0yMDAzMTEwMDAtMDAwMTU |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA5Ny8wMDAwMDU0Mi0yMDAzMTEwMDAtMDAwMTU |
| institution |
DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 |
| imprint |
Ovid Technologies (Wolters Kluwer Health), 2003 |
| imprint_str_mv |
Ovid Technologies (Wolters Kluwer Health), 2003 |
| issn |
0003-3022 |
| issn_str_mv |
0003-3022 |
| language |
English |
| mega_collection |
Ovid Technologies (Wolters Kluwer Health) (CrossRef) |
| match_str |
benkwitz2003lidocaineenhancesgaiproteinfunction |
| publishDateSort |
2003 |
| publisher |
Ovid Technologies (Wolters Kluwer Health) |
| recordtype |
ai |
| record_format |
ai |
| series |
Anesthesiology |
| source_id |
49 |
| title |
Lidocaine Enhances GαiProtein Function |
| title_unstemmed |
Lidocaine Enhances GαiProtein Function |
| title_full |
Lidocaine Enhances GαiProtein Function |
| title_fullStr |
Lidocaine Enhances GαiProtein Function |
| title_full_unstemmed |
Lidocaine Enhances GαiProtein Function |
| title_short |
Lidocaine Enhances GαiProtein Function |
| title_sort |
lidocaine enhances gαiprotein function |
| topic |
Anesthesiology and Pain Medicine |
| url |
http://dx.doi.org/10.1097/00000542-200311000-00015 |
| publishDate |
2003 |
| physical |
1093-1101 |
| description |
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Local anesthetics inhibit several G protein-coupled receptors by interaction with the Galphaq protein subunit. It is not known whether this effect on G protein function can be extrapolated to other classes of G proteins. The authors investigated interactions of lidocaine with the human adenosine 1 receptor (hA1R)-coupled signaling pathway. Activated A1Rs couple to adenylate cyclase via the pertussis toxin sensitive Galphai protein, thereby decreasing cyclic adenosine monophosphate formation. A1Rs are widely expressed and abundant in the spinal cord, brain, and heart. Interactions of LAs with the hA1R-coupled transduction cascade therefore might produce a broad range of clinically relevant effects.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>The function of hA1Rs stably expressed in Chinese hamster ovary cells was determined with assays of cyclic adenosine monophosphate, receptor binding, and guanosine diphosphate/guanosine triphosphate gamma35S exchange by using reconstituted defined G protein subunits. Involvement of phosphodiesterase and Galphai was characterized by using the phosphodiesterase inhibitor rolipram and pertussis toxin, respectively.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>Lidocaine (10-9-10-1 M) had no significant effects on agonist or antagonist binding to the hA1R or on receptor-G protein interactions. However, cyclic adenosine monophosphate levels were reduced significantly to 50% by the LAs, even in the absence of an A1R agonist or presence of an A1R antagonist. This effect was unaffected by rolipram (10 mum), but abolished completely by pretreatment with pertussis toxin, which inactivates the Galphai protein. Therefore, the main target site for LAs in this pathway is located upstream from adenylate cyclase.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Lidocaine potentiates Galphai-coupled A1R signaling by reducing cyclic adenosine monophosphate production. The study suggests an interaction site for LAs in a Galphai-coupled signaling pathway, with the Galphai protein representing the prime candidate. Taken together with previous results showing inhibitory LA interactions on the Galphaq protein subunit, the data in the current study support the hypothesis that specific G protein subunits represent alternative sites of LA action.</jats:p>
</jats:sec> |
| container_issue |
5 |
| container_start_page |
1093 |
| container_title |
Anesthesiology |
| container_volume |
99 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792335500445483012 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T14:45:16.407Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Lidocaine+Enhances+G%CE%B1iProtein+Function&rft.date=2003-11-01&genre=article&issn=0003-3022&volume=99&issue=5&spage=1093&epage=1101&pages=1093-1101&jtitle=Anesthesiology&atitle=Lidocaine+Enhances+G%CE%B1iProtein+Function&aulast=Hollmann&aufirst=Markus%C2%A0W.&rft_id=info%3Adoi%2F10.1097%2F00000542-200311000-00015&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792335500445483012 |
| author | Benkwitz, Claudia, Garrison, James C., Linden, Joel, Durieux, Marcel E., Hollmann, Markus W. |
| author_facet | Benkwitz, Claudia, Garrison, James C., Linden, Joel, Durieux, Marcel E., Hollmann, Markus W., Benkwitz, Claudia, Garrison, James C., Linden, Joel, Durieux, Marcel E., Hollmann, Markus W. |
| author_sort | benkwitz, claudia |
| container_issue | 5 |
| container_start_page | 1093 |
| container_title | Anesthesiology |
| container_volume | 99 |
| description | <jats:sec> <jats:title>Background</jats:title> <jats:p>Local anesthetics inhibit several G protein-coupled receptors by interaction with the Galphaq protein subunit. It is not known whether this effect on G protein function can be extrapolated to other classes of G proteins. The authors investigated interactions of lidocaine with the human adenosine 1 receptor (hA1R)-coupled signaling pathway. Activated A1Rs couple to adenylate cyclase via the pertussis toxin sensitive Galphai protein, thereby decreasing cyclic adenosine monophosphate formation. A1Rs are widely expressed and abundant in the spinal cord, brain, and heart. Interactions of LAs with the hA1R-coupled transduction cascade therefore might produce a broad range of clinically relevant effects.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The function of hA1Rs stably expressed in Chinese hamster ovary cells was determined with assays of cyclic adenosine monophosphate, receptor binding, and guanosine diphosphate/guanosine triphosphate gamma35S exchange by using reconstituted defined G protein subunits. Involvement of phosphodiesterase and Galphai was characterized by using the phosphodiesterase inhibitor rolipram and pertussis toxin, respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Lidocaine (10-9-10-1 M) had no significant effects on agonist or antagonist binding to the hA1R or on receptor-G protein interactions. However, cyclic adenosine monophosphate levels were reduced significantly to 50% by the LAs, even in the absence of an A1R agonist or presence of an A1R antagonist. This effect was unaffected by rolipram (10 mum), but abolished completely by pretreatment with pertussis toxin, which inactivates the Galphai protein. Therefore, the main target site for LAs in this pathway is located upstream from adenylate cyclase.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Lidocaine potentiates Galphai-coupled A1R signaling by reducing cyclic adenosine monophosphate production. The study suggests an interaction site for LAs in a Galphai-coupled signaling pathway, with the Galphai protein representing the prime candidate. Taken together with previous results showing inhibitory LA interactions on the Galphaq protein subunit, the data in the current study support the hypothesis that specific G protein subunits represent alternative sites of LA action.</jats:p> </jats:sec> |
| doi_str_mv | 10.1097/00000542-200311000-00015 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA5Ny8wMDAwMDU0Mi0yMDAzMTEwMDAtMDAwMTU |
| imprint | Ovid Technologies (Wolters Kluwer Health), 2003 |
| imprint_str_mv | Ovid Technologies (Wolters Kluwer Health), 2003 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
| issn | 0003-3022 |
| issn_str_mv | 0003-3022 |
| language | English |
| last_indexed | 2024-03-01T14:45:16.407Z |
| match_str | benkwitz2003lidocaineenhancesgaiproteinfunction |
| mega_collection | Ovid Technologies (Wolters Kluwer Health) (CrossRef) |
| physical | 1093-1101 |
| publishDate | 2003 |
| publishDateSort | 2003 |
| publisher | Ovid Technologies (Wolters Kluwer Health) |
| record_format | ai |
| recordtype | ai |
| series | Anesthesiology |
| source_id | 49 |
| spelling | Benkwitz, Claudia Garrison, James C. Linden, Joel Durieux, Marcel E. Hollmann, Markus W. 0003-3022 Ovid Technologies (Wolters Kluwer Health) Anesthesiology and Pain Medicine http://dx.doi.org/10.1097/00000542-200311000-00015 <jats:sec> <jats:title>Background</jats:title> <jats:p>Local anesthetics inhibit several G protein-coupled receptors by interaction with the Galphaq protein subunit. It is not known whether this effect on G protein function can be extrapolated to other classes of G proteins. The authors investigated interactions of lidocaine with the human adenosine 1 receptor (hA1R)-coupled signaling pathway. Activated A1Rs couple to adenylate cyclase via the pertussis toxin sensitive Galphai protein, thereby decreasing cyclic adenosine monophosphate formation. A1Rs are widely expressed and abundant in the spinal cord, brain, and heart. Interactions of LAs with the hA1R-coupled transduction cascade therefore might produce a broad range of clinically relevant effects.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The function of hA1Rs stably expressed in Chinese hamster ovary cells was determined with assays of cyclic adenosine monophosphate, receptor binding, and guanosine diphosphate/guanosine triphosphate gamma35S exchange by using reconstituted defined G protein subunits. Involvement of phosphodiesterase and Galphai was characterized by using the phosphodiesterase inhibitor rolipram and pertussis toxin, respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Lidocaine (10-9-10-1 M) had no significant effects on agonist or antagonist binding to the hA1R or on receptor-G protein interactions. However, cyclic adenosine monophosphate levels were reduced significantly to 50% by the LAs, even in the absence of an A1R agonist or presence of an A1R antagonist. This effect was unaffected by rolipram (10 mum), but abolished completely by pretreatment with pertussis toxin, which inactivates the Galphai protein. Therefore, the main target site for LAs in this pathway is located upstream from adenylate cyclase.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Lidocaine potentiates Galphai-coupled A1R signaling by reducing cyclic adenosine monophosphate production. The study suggests an interaction site for LAs in a Galphai-coupled signaling pathway, with the Galphai protein representing the prime candidate. Taken together with previous results showing inhibitory LA interactions on the Galphaq protein subunit, the data in the current study support the hypothesis that specific G protein subunits represent alternative sites of LA action.</jats:p> </jats:sec> Lidocaine Enhances GαiProtein Function Anesthesiology |
| spellingShingle | Benkwitz, Claudia, Garrison, James C., Linden, Joel, Durieux, Marcel E., Hollmann, Markus W., Anesthesiology, Lidocaine Enhances GαiProtein Function, Anesthesiology and Pain Medicine |
| title | Lidocaine Enhances GαiProtein Function |
| title_full | Lidocaine Enhances GαiProtein Function |
| title_fullStr | Lidocaine Enhances GαiProtein Function |
| title_full_unstemmed | Lidocaine Enhances GαiProtein Function |
| title_short | Lidocaine Enhances GαiProtein Function |
| title_sort | lidocaine enhances gαiprotein function |
| title_unstemmed | Lidocaine Enhances GαiProtein Function |
| topic | Anesthesiology and Pain Medicine |
| url | http://dx.doi.org/10.1097/00000542-200311000-00015 |