Phosphodiesterase Type 5 Inhibitors Greatly Affect Physicochemical Properties of Model Lipid Membranes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Membrane Boundary Potential Measurements
2.3. Membrane Dipole Potential Measurements
2.4. Differential Scanning Microcalorimetry
2.5. Reconstitution of Ion Channels into Planar Lipid Bilayers
3. Results and Discussion
3.1. The Effects of PDE-5 Inhibitors on the Electrical Properties of Lipid Bilayers and Voltage-Sensitive Ion Channels
3.2. The Effect of PDE-5 Inhibitors on the Lipid Packing and Ion Channels Sensitive to Membrane Curvature Stress
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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PDE-5 Inhibitor | Chemical Structure | Charge * | LogPo/w | µ, D |
---|---|---|---|---|
sildenafil | −0.34 | 2.7 [21] 3.18 [22] | 6.4 [23] | |
vardenafil | 0.06 | 3.64 [21] | na | |
tadalafil | 0 | 2.4 [24] | 2.67–3.07 [25] |
POPC | POPC/Chol | DPPC | |||||
---|---|---|---|---|---|---|---|
−Δφb(max), mV | K, μM | −Δφd(max), mV | −Δφb(max), mV | K, μM | −∆Tm, °C | ∆T1/2, °C | |
sildenafil | 67 ± 10 | 21 ± 4 | 91 ± 20 | 83 ± 13 | 30 ± 2 | 1.4 ± 0.4 | 0.7 ± 0.2 |
vardenafil | 84 ± 19 | 17 ± 2 | 84 ± 23 | 71 ± 10 | 31 ± 3 | 0.9 ± 0.4 | 0.7 ± 0.3 |
tadalafil | 74 ± 9 | 3 ± 1 | 78 ± 11 | 86 ± 10 | 10 ± 2 | 0.2 ± 0.1 | 0.1 ± 0.1 |
gsc, pS | I∞/I∞0 | |
---|---|---|
control | 22 ± 1 | – |
sildenafil | 28 ± 1 | 11.1 ± 0.9 |
vardenafil | 29 ± 2 | 12.7 ± 3.2 |
tadalafil | 26 ± 2 | 1.9 ± 0.7 |
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Zakharova, A.A.; Efimova, S.S.; Ostroumova, O.S. Phosphodiesterase Type 5 Inhibitors Greatly Affect Physicochemical Properties of Model Lipid Membranes. Membranes 2021, 11, 893. https://doi.org/10.3390/membranes11110893
Zakharova AA, Efimova SS, Ostroumova OS. Phosphodiesterase Type 5 Inhibitors Greatly Affect Physicochemical Properties of Model Lipid Membranes. Membranes. 2021; 11(11):893. https://doi.org/10.3390/membranes11110893
Chicago/Turabian StyleZakharova, Anastasiia A., Svetlana S. Efimova, and Olga S. Ostroumova. 2021. "Phosphodiesterase Type 5 Inhibitors Greatly Affect Physicochemical Properties of Model Lipid Membranes" Membranes 11, no. 11: 893. https://doi.org/10.3390/membranes11110893