α1-and β-adrenergic antagonist labetalol induces morphological changes in human erythrocytes
2018
Zambrano, Pablo | Suwalsky, Mario | Jemiola-Rzeminska, Malgorzata | Strzałka, Kazimierz
Labetalol is one of the most used drugs for the treatment of hypertension. This molecule is able to bind to both alpha-1 (α1) and beta (β) adrenergic receptors present in vascular smooth muscle among other tissues. It has been determined that human erythrocytes possess both alpha receptors and beta-adrenergic receptors expressed on their surface. The objective of this work was to study the effect of labetalol on the morphology of human erythrocytes. To accomplish this goal, human erythrocytes and model membranes built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were used. These lipid species are present in the outer and inner monolayers of the red blood cell membrane, respectively. Our findings obtained by X-ray diffraction and differential scanning calorimetry (DSC) indicate that labetalol interacted with both lipids in a process dependent on concentration. In fact, at low concentrations labetalol preferentially interacted with DMPE. On the other hand, results obtained by scanning electron microscopy (SEM) showed that labetalol alters the normal biconcave form of erythrocytes to stomatocytes and knizocytes (cells with one or more cavities, respectively). According to the bilayers couple hypothesis, this result implied that the drug inserted in the inner monolayer of the human erythrocyte membrane.
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