Local Anesthetics, Antipsychotic Phenothiazines, and Cationic Surfactants Shut Down Intracellular Reactions through Membrane Perturbation in Yeast
Abstract
High osmolarity and glucose deprivation cause rapid shutdowns of both actin polarization and translation initiation in yeast. Like these stresses, administration of local anesthetics and of antipsychotic phenothiazines caused similar responses. All these drugs have amphiphilic structures and formed emulsions and permeabilized the cell membrane, indicating that they have the same features as a surfactant. Consistently with this, surfactants induced responses similar to those of local anesthetics and phenothiazines. Benzethonium chloride, a cationic surfactant, showed a more potent shutdown activity than phenothiazines, whereas SDS, an anionic surfactant, transiently depolarized actin without inhibiting translation initiation, suggesting that a cationic charge in the amphiphile is important to the shutdown of both reactions. The clinical drugs and the cationic surfactants at low concentrations caused shutdown without membrane permeabilization, suggesting that these compounds and stresses activate shutdown, via perturbation rather than disruption of the cell membrane.
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The antipsychotic phenothiazine and the antidepressant nortriptyline have been reported to disrupt cell membranes.
“The antipsychotic phenothiazine and the antidepressant nortriptyline have also been reported to disrupt cell membranes [72,104,105].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [104]
The cell lysis induced by nortriptyline, local anesthetics, and antipsychotic phenothiazine is related to their amphiphilic structures and surfactant activity, which disturb cell membrane functionality.
“This phenomenon is related to their amphiphilic structures and their surfactant activity, which are able to disturb cell membrane functionality [11,13].”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [13]
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- Authors
- UESONO, Y., ARAKI, T., & TOH-E, A.
- Affiliations
- The University of Tokyo (JP)
- Saitama Medical University (JP)
- ORCID
- UESONO, Yukifumi
- Venue
- Bioscience, Biotechnology, and Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11-23
- Volume
- 72
- Issue
- 11
- Pages
- 2884-2894
- ISSN
- 0916-8451 (ISSN-L)
- 1347-6947
- OpenAlex
- W2143150010
- Cited by
- 36
- References
- 34
- Citations by year
- 2023: 21 · 2021: 2 · 2020: 2 · 2017: 1 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioscience Biotechnology and Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- local anesthetics, phenothiazines, cationic surfactants, benzethonium chloride, sodium dodecyl sulfate, membrane perturbation, actin polarization, translation initiation, osmotic stress, glucose deprivation, yeast, amphiphilic drugs, membrane permeabilization
- MeSH terms
- Anesthetics, Cell Membrane, Humans, Osmolar Concentration, Phenothiazines, Saccharomyces cerevisiae, Surface-Active Agents, Time Factors, Antipsychotic Agents, Intracellular Space
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