α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1)
Methoxamine (Mox) is a well-known α1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sciendo
2023-06-01
|
| Series: | Acta Pharmaceutica |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/acph-2023-0012 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832546411474845696 |
|---|---|
| author | Kohutova Aneta Münzova Dita Pešl Martin Rotrekl Vladimir |
| author_facet | Kohutova Aneta Münzova Dita Pešl Martin Rotrekl Vladimir |
| author_sort | Kohutova Aneta |
| collection | DOAJ |
| description | Methoxamine (Mox) is a well-known α1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as an inhibitor of base excision repair (BER). The effect is mediated by the inhibition of apurinic/apyrimidinic endonuclease APE1. We link this observation to our previous report showing the biologically relevant effect of Mox on BER – prevention of converting oxidative DNA base damage to double-stranded breaks. We demonstrate that its effect is weaker, but still significant when compared to a known BER inhibitor methoxyamine (MX). We further determined Mox’s relative IC50 at 19 mmol L−1, demonstrating a significant effect of Mox on APE1 activity in clinically relevant concentrations. |
| format | Article |
| id | doaj-art-90fe577c187f44d0a6f33f520cb887c2 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2023-06-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-90fe577c187f44d0a6f33f520cb887c22025-02-03T07:04:13ZengSciendoActa Pharmaceutica1846-95582023-06-0173228129110.2478/acph-2023-0012α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1)Kohutova Aneta0Münzova Dita1Pešl Martin2Rotrekl Vladimir31Masaryk University, Faculty of Medicine, Department of Biology625 00, Brno, Czech Republic1Masaryk University, Faculty of Medicine, Department of Biology625 00, Brno, Czech Republic1Masaryk University, Faculty of Medicine, Department of Biology625 00, Brno, Czech Republic1Masaryk University, Faculty of Medicine, Department of Biology625 00, Brno, Czech RepublicMethoxamine (Mox) is a well-known α1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as an inhibitor of base excision repair (BER). The effect is mediated by the inhibition of apurinic/apyrimidinic endonuclease APE1. We link this observation to our previous report showing the biologically relevant effect of Mox on BER – prevention of converting oxidative DNA base damage to double-stranded breaks. We demonstrate that its effect is weaker, but still significant when compared to a known BER inhibitor methoxyamine (MX). We further determined Mox’s relative IC50 at 19 mmol L−1, demonstrating a significant effect of Mox on APE1 activity in clinically relevant concentrations.https://doi.org/10.2478/acph-2023-0012methoxaminebase excision repairapurinic/apyrimidinic endonuclease ape1α1-adrenoceptor agonist |
| spellingShingle | Kohutova Aneta Münzova Dita Pešl Martin Rotrekl Vladimir α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1) Acta Pharmaceutica methoxamine base excision repair apurinic/apyrimidinic endonuclease ape1 α1-adrenoceptor agonist |
| title | α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1) |
| title_full | α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1) |
| title_fullStr | α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1) |
| title_full_unstemmed | α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1) |
| title_short | α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1) |
| title_sort | α1 adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic apyrimidinic endonuclease 1 ape1 |
| topic | methoxamine base excision repair apurinic/apyrimidinic endonuclease ape1 α1-adrenoceptor agonist |
| url | https://doi.org/10.2478/acph-2023-0012 |
| work_keys_str_mv | AT kohutovaaneta a1adrenoceptoragonistmethoxamineinhibitsbaseexcisionrepairviainhibitionofapurinicapyrimidinicendonuclease1ape1 AT munzovadita a1adrenoceptoragonistmethoxamineinhibitsbaseexcisionrepairviainhibitionofapurinicapyrimidinicendonuclease1ape1 AT peslmartin a1adrenoceptoragonistmethoxamineinhibitsbaseexcisionrepairviainhibitionofapurinicapyrimidinicendonuclease1ape1 AT rotreklvladimir a1adrenoceptoragonistmethoxamineinhibitsbaseexcisionrepairviainhibitionofapurinicapyrimidinicendonuclease1ape1 |