Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction
Damage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, v...
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| Format: | Article |
| Language: | English |
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Oles Honchar Dnipro National University
2017-01-01
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| Series: | Regulatory Mechanisms in Biosystems |
| Subjects: | |
| Online Access: | https://medicine.dp.ua/index.php/med/article/view/300 |
| _version_ | 1811193055528615936 |
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| author | P. A. Virych O. V. Shelyuk T. A. Kabanova O. I. Khalimova V. S. Martynyuk V. I. Pavlovsky S. A. Andronati |
| author_facet | P. A. Virych O. V. Shelyuk T. A. Kabanova O. I. Khalimova V. S. Martynyuk V. I. Pavlovsky S. A. Andronati |
| author_sort | P. A. Virych |
| collection | DOAJ |
| description | Damage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, vascular tone and other functions. A new group of substances that may used for this purpose are 3-substituted 1,4-benzdiazepinones. We analyzed the effect of 3-aryl amino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction of the stomach in the presence of calcium channel blockers verapamil (1 μM) and gadolinium (300 μM). The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in the incubation solution were 10–6 M. Data processing on the dynamics of contraction was performed according to the method of T. Burdyha and S. Kosterin. Statistically significant changes were found for MX-1828. This compound reduced the maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of Gd3+ and verapamil by 19.3% and 32.0%, respectively. Also, MX-1828 demonstrated effects similar to those of the competitive inhibitor bradykinin B2-receptor – des-Arg9-bradykinin-acetate, which is possible evidence of its interaction with the receptor or signal transduction pathways. MX-1828 additionally reduced the maximum normalized rate of relaxation by 6.2% in the presence of Gd3+. This effect was demonstrated for MX-1906 in the presence of verapamil with additional reduction of the maximal normalized rate of relaxation, which was 26.4%. The results suggest the presence of inhibitory interaction between MX-1828 and kinin-kallikrein system receptors or signal transduction pathways. The effects which were found for MX-1906 require further studies to clarify the mechanisms of influence on bradykinin-induced smooth muscle contraction. |
| first_indexed | 2024-04-12T00:02:04Z |
| format | Article |
| id | doaj.art-a80f4e671fd44c01b9e903583416e0e7 |
| institution | Directory Open Access Journal |
| issn | 2519-8521 |
| language | English |
| last_indexed | 2024-04-12T00:02:04Z |
| publishDate | 2017-01-01 |
| publisher | Oles Honchar Dnipro National University |
| record_format | Article |
| series | Regulatory Mechanisms in Biosystems |
| spelling | doaj.art-a80f4e671fd44c01b9e903583416e0e72022-12-22T03:56:12ZengOles Honchar Dnipro National UniversityRegulatory Mechanisms in Biosystems2519-85212017-01-0181303510.15421/021706262Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contractionP. A. Virych0O. V. Shelyuk1T. A. Kabanova2O. I. Khalimova3V. S. Martynyuk4V. I. Pavlovsky5S. A. Andronati6Taras Shevchenko National University of KyivTaras Shevchenko National University of KyivO. V. Bogatsky Physico-Chemical InstituteO. V. Bogatsky Physico-Chemical InstituteTaras Shevchenko National University of KyivO. V. Bogatsky Physico-Chemical InstituteO. V. Bogatsky Physico-Chemical InstituteDamage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, vascular tone and other functions. A new group of substances that may used for this purpose are 3-substituted 1,4-benzdiazepinones. We analyzed the effect of 3-aryl amino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction of the stomach in the presence of calcium channel blockers verapamil (1 μM) and gadolinium (300 μM). The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in the incubation solution were 10–6 M. Data processing on the dynamics of contraction was performed according to the method of T. Burdyha and S. Kosterin. Statistically significant changes were found for MX-1828. This compound reduced the maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of Gd3+ and verapamil by 19.3% and 32.0%, respectively. Also, MX-1828 demonstrated effects similar to those of the competitive inhibitor bradykinin B2-receptor – des-Arg9-bradykinin-acetate, which is possible evidence of its interaction with the receptor or signal transduction pathways. MX-1828 additionally reduced the maximum normalized rate of relaxation by 6.2% in the presence of Gd3+. This effect was demonstrated for MX-1906 in the presence of verapamil with additional reduction of the maximal normalized rate of relaxation, which was 26.4%. The results suggest the presence of inhibitory interaction between MX-1828 and kinin-kallikrein system receptors or signal transduction pathways. The effects which were found for MX-1906 require further studies to clarify the mechanisms of influence on bradykinin-induced smooth muscle contraction.https://medicine.dp.ua/index.php/med/article/view/3003-substituted 1,4-benzodiazepinesbradykininkinin-kallikrein systemmaximal normalized rate |
| spellingShingle | P. A. Virych O. V. Shelyuk T. A. Kabanova O. I. Khalimova V. S. Martynyuk V. I. Pavlovsky S. A. Andronati Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction Regulatory Mechanisms in Biosystems 3-substituted 1,4-benzodiazepines bradykinin kinin-kallikrein system maximal normalized rate |
| title | Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction |
| title_full | Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction |
| title_fullStr | Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction |
| title_full_unstemmed | Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction |
| title_short | Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction |
| title_sort | effect of 3 arylamino 1 2 dihydro 3h 1 4 benzodiazepine 2 ones on the bradykinin induced smooth muscle contraction |
| topic | 3-substituted 1,4-benzodiazepines bradykinin kinin-kallikrein system maximal normalized rate |
| url | https://medicine.dp.ua/index.php/med/article/view/300 |
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