Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations
| ISSN: |
0003-9861
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|---|---|
| Source: |
Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
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| Topics: |
Biology
Chemistry and Pharmacology
Physics
|
| Type of Medium: |
Electronic Resource
|
| URL: |
| _version_ | 1798292194652585984 |
|---|---|
| autor | Koul, O. Hauser, G. |
| autorsonst | Koul, O. Hauser, G. |
| book_url | http://dx.doi.org/10.1016/0003-9861(87)90199-8 |
| datenlieferant | nat_lic_papers |
| fussnote | The effects of three cationic amphiphilic drugs on rat brain cytosolic phosphatidate phosphohydrolase and their mechanisms of action were studied utilizing membranebound, emulsified, and emulsified sonicated phosphatidate as substrates. With the membrane-bound substrate, chlorpromazine, desmethylimipramine, and propranolol inhibited the activity in a dose-dependent fashion with an IC"5"0 of 30-50 μm. In the presence of the emulsified substrate, chlorpromazine was a more potent inhibitor than desmethylimipramine or propranolol but 200 μm was needed for 50% inhibition of activity. Addition of heat-inactivated microsomes to the emulsified substrate, to simulate the conditions with the membrane-bound substrate, did not alter this value. Both Mg^2^+ and Ca^2^+ stimulated the enzyme activity but only Ca^2^+ counteracted the effect of chlorpromazine. Kinetic studies indicate that chlorpromazine acts as a noncompetitive inhibitor of the enzyme. Emulsified sonicated phosphatidate was a good substrate at low (〈10 μm) concentrations. It was a poor substrate at 1 mm, but at this concentration chlorpromazine stimulated the activity instead of inhibiting. This drug altered the integrity of phosphatidate vesicle membranes as visualized by electron microscopy. The different results obtained with the three types of substrate indicate the importance of the configuration of phosphatidate for the expression of enzyme activity and for its susceptibility to the action of cationic amphiphilic drugs. |
| hauptsatz | hsatz_simple |
| identnr | NLZ183424131 |
| issn | 0003-9861 |
| journal_name | Archives of Biochemistry and Biophysics |
| materialart | 1 |
| package_name | Elsevier |
| publikationsort | Amsterdam |
| publisher | Elsevier |
| reference | 253 (1987), S. 453-461 |
| search_space | articles |
| shingle_author_1 | Koul, O. Hauser, G. |
| shingle_author_2 | Koul, O. Hauser, G. |
| shingle_author_3 | Koul, O. Hauser, G. |
| shingle_author_4 | Koul, O. Hauser, G. |
| shingle_catch_all_1 | Koul, O. Hauser, G. Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations 0003-9861 00039861 Elsevier |
| shingle_catch_all_2 | Koul, O. Hauser, G. Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations 0003-9861 00039861 Elsevier |
| shingle_catch_all_3 | Koul, O. Hauser, G. Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations 0003-9861 00039861 Elsevier |
| shingle_catch_all_4 | Koul, O. Hauser, G. Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations 0003-9861 00039861 Elsevier |
| shingle_title_1 | Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations |
| shingle_title_2 | Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations |
| shingle_title_3 | Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations |
| shingle_title_4 | Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations |
| sigel_instance_filter | dkfz geomar wilbert ipn albert fhp |
| source_archive | Elsevier Journal Backfiles on ScienceDirect 1907 - 2002 |
| timestamp | 2024-05-06T08:44:38.534Z |
| titel | Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations |
| titel_suche | Modulation of rat brain cytosolic phosphatidate phosphohydrolase: Effect of cationic amphiphilic drugs and divalent cations The effects of three cationic amphiphilic drugs on rat brain cytosolic phosphatidate phosphohydrolase and their mechanisms of action were studied utilizing membranebound, emulsified, and emulsified sonicated phosphatidate as substrates. With the membrane-bound substrate, chlorpromazine, desmethylimipramine, and propranolol inhibited the activity in a dose-dependent fashion with an IC"5"0 of 30-50 μm. In the presence of the emulsified substrate, chlorpromazine was a more potent inhibitor than desmethylimipramine or propranolol but 200 μm was needed for 50% inhibition of activity. Addition of heat-inactivated microsomes to the emulsified substrate, to simulate the conditions with the membrane-bound substrate, did not alter this value. Both Mg^2^+ and Ca^2^+ stimulated the enzyme activity but only Ca^2^+ counteracted the effect of chlorpromazine. Kinetic studies indicate that chlorpromazine acts as a noncompetitive inhibitor of the enzyme. Emulsified sonicated phosphatidate was a good substrate at low (〈10 μm) concentrations. It was a poor substrate at 1 mm, but at this concentration chlorpromazine stimulated the activity instead of inhibiting. This drug altered the integrity of phosphatidate vesicle membranes as visualized by electron microscopy. The different results obtained with the three types of substrate indicate the importance of the configuration of phosphatidate for the expression of enzyme activity and for its susceptibility to the action of cationic amphiphilic drugs. |
| topic | W V U |
| uid | nat_lic_papers_NLZ183424131 |