Alteration of membrane permeability by amphotericin B

Area of Science:

• Physiology
• Pharmacology
• Membrane Transport

Background:

• Amphotericin B (AmB) is an antifungal agent known to affect cell membranes.
• Understanding its interaction with epithelial tissues is crucial for its therapeutic application and potential side effects.

Purpose of the Study:

• To investigate the effect of Amphotericin B on sodium transport across the frog skin.
• To determine the side of application and the mechanism involved in AmB-induced changes in sodium permeability.

Main Methods:

• Experiments were conducted on isolated frog (Rana pipiens) skin.
• Amphotericin B was applied to either the corium or epidermal side of the skin.
• Sodium transport was measured using electrophysiological techniques.
• Inhibitors like amiloride and ouabain were used to probe the transport pathway.
• Effects of pH and antidiuretic hormone were also assessed.

Main Results:

• Amphotericin B significantly increased unidirectional Na transport and net transcellular sodium movements when applied to the corium side.
• The effect was not observed when AmB was applied to the epidermal surface.
• Pretreatment with amiloride, ouabain, or mucosal sodium substitution blocked the AmB response.
• Changes in pH reduced the permeability alterations induced by AmB.
• AmB did not affect the sodium transport stimulated by antidiuretic hormone.

Conclusions:

• Amphotericin B interacts with the frog skin from the corium side, specifically enhancing transepithelial sodium transport.
• The increased transport occurs through the existing sodium pathway, suggesting modulation rather than creation of new channels.
• The findings provide insight into the localized effects of Amphotericin B on epithelial sodium transport mechanisms.