α1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes
α1-Acid glycoprotein (AAG) is an acute phase protein capable of binding basic drugs. This action explains its reversal of sodium channel blockade by drugs such as amitriptyline and quinidine. We report here the reversal of cocaine-induced sodium channel blockade by AAG. The sodium channel blocking p...
| Main Authors: | , , |
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| Format: | Journal article |
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Elsevier
2006
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| _version_ | 1797078665095282688 |
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| author | Ma, Y Peters, N Henry, J |
| author_facet | Ma, Y Peters, N Henry, J |
| author_sort | Ma, Y |
| collection | OXFORD |
| description | α1-Acid glycoprotein (AAG) is an acute phase protein capable of binding basic drugs. This action explains its reversal of sodium channel blockade by drugs such as amitriptyline and quinidine. We report here the reversal of cocaine-induced sodium channel blockade by AAG. The sodium channel blocking property of cocaine is a major mechanism behind cocaine-induced sudden cardiac death, since sodium channels play a key role in the initiation and regulation of the heart beat. Voltage-gated sodium current (INa) was recorded using whole-cell patch-clamp techniques. Guinea-pig cardiac ventricular myocytes were isolated and continuously perfused at room temperature with physiological solutions. At concentrations ranging from 5 to 320 μM cocaine showed a dose-dependent and reversible blockade of INa with an IC50 of 45.9 μM. The addition of equimolar amounts of AAG to cocaine produced almost complete reversal of cocaine's effects, suggesting a single binding site for cocaine on the AAG molecule. With changes of peak INa normalized against control as 1, cocaine at 20 and 40 μM reduced INa to 0.62 ± 0.042 (n = 6) and 0.57 ± 0.052 (n = 9), respectively, and the addition of an equimolar concentration of AAG reversed INa to 0.86 ± 0.022 and 0.91 ± 0.060, respectively. In conclusion: AAG reverses cocaine-induced sodium channel blockade in a dose-dependent manner, indicating a therapeutic potential to reverse acute cocaine cardiac toxicity. |
| first_indexed | 2024-03-07T00:35:00Z |
| format | Journal article |
| id | oxford-uuid:8118d12f-13ed-4479-a12a-996fa54cc858 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:35:00Z |
| publishDate | 2006 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:8118d12f-13ed-4479-a12a-996fa54cc8582022-03-26T21:27:59Zα1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8118d12f-13ed-4479-a12a-996fa54cc858Symplectic Elements at OxfordElsevier2006Ma, YPeters, NHenry, Jα1-Acid glycoprotein (AAG) is an acute phase protein capable of binding basic drugs. This action explains its reversal of sodium channel blockade by drugs such as amitriptyline and quinidine. We report here the reversal of cocaine-induced sodium channel blockade by AAG. The sodium channel blocking property of cocaine is a major mechanism behind cocaine-induced sudden cardiac death, since sodium channels play a key role in the initiation and regulation of the heart beat. Voltage-gated sodium current (INa) was recorded using whole-cell patch-clamp techniques. Guinea-pig cardiac ventricular myocytes were isolated and continuously perfused at room temperature with physiological solutions. At concentrations ranging from 5 to 320 μM cocaine showed a dose-dependent and reversible blockade of INa with an IC50 of 45.9 μM. The addition of equimolar amounts of AAG to cocaine produced almost complete reversal of cocaine's effects, suggesting a single binding site for cocaine on the AAG molecule. With changes of peak INa normalized against control as 1, cocaine at 20 and 40 μM reduced INa to 0.62 ± 0.042 (n = 6) and 0.57 ± 0.052 (n = 9), respectively, and the addition of an equimolar concentration of AAG reversed INa to 0.86 ± 0.022 and 0.91 ± 0.060, respectively. In conclusion: AAG reverses cocaine-induced sodium channel blockade in a dose-dependent manner, indicating a therapeutic potential to reverse acute cocaine cardiac toxicity. |
| spellingShingle | Ma, Y Peters, N Henry, J α1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes |
| title | α1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes |
| title_full | α1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes |
| title_fullStr | α1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes |
| title_full_unstemmed | α1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes |
| title_short | α1-Acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes |
| title_sort | α1 acid glycoprotein reverses cocaine induced sodium channel blockade in cardiac myocytes |
| work_keys_str_mv | AT may a1acidglycoproteinreversescocaineinducedsodiumchannelblockadeincardiacmyocytes AT petersn a1acidglycoproteinreversescocaineinducedsodiumchannelblockadeincardiacmyocytes AT henryj a1acidglycoproteinreversescocaineinducedsodiumchannelblockadeincardiacmyocytes |