In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner
| Autor: | Erlend Hodneland, Holm Holmsen, Ramadhan Oruch, Ian F. Pryme |
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| Rok vydání: | 2009 |
| Předmět: |
PPI cycle
Biophysics Phospholipid Pharmacology Citalopram Biochemistry chemistry.chemical_compound Phospholipase A2 Intercalation medicine Platelet Receptor PLA2 Diazepam biology Phospholipase C Psychotrophic drugs Cell Biology Promethazine Langmuir technique chemistry biology.protein Original Article lipids (amino acids peptides and proteins) Substrate availability Human platelets MLC medicine.drug |
| Zdroj: | Journal of Chemical Biology |
| ISSN: | 1864-6166 1864-6158 |
| Popis: | Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs' intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A(2) (PLA(2)) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA( 2 ) activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA(2) and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects. |
| Databáze: | OpenAIRE |
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