AN EXTENSION OF pA PRINCIPLE TO THE POTENTIATION OF DRUG EFFECTS, AND ITS APPLICATION TO THE BIOLOGICAL ASSAY OF SOME ANTICHOLINESTERASES AND CARDENOLIDES

Ishikawa, Naohisa; Ichikawa, Tomohiro; Tsuru, Hiromichi; Shigei, Tatsuro

doi:10.1254/jjp.30.49

Cited by 1 publication

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“…The polarization changes were expressed as a percentage of the maximum increase induced by 200 μM capsaicin. IC 50 and pA2 were calculated according to Science GatewayCell Biology Protocols [ 43 ] and a report of Ishikawa et al [ 44 ], respectively.…”

Section: Methodsmentioning

confidence: 99%

Membrane Interactivity of Capsaicin Antagonized by Capsazepine

Mizogami

Tsuchiya

2022

IJMS

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Although the pharmacological activity of capsaicin has been explained by its specific binding to transient receptor potential vanilloid type 1, the amphiphilic structure of capsaicin may enable it to act on lipid bilayers. From a mechanistic point of view, we investigated whether capsaicin and its antagonist capsazepine interact with biomimetic membranes, and how capsazepine influences the membrane effect of capsaicin. Liposomal phospholipid membranes and neuro-mimetic membranes were prepared with 1,2-dipalmitoylphosphatidylcholine and with 1-palmitoyl-2-oleoylphosphatidylcholine and sphingomyelin plus cholesterol, respectively. These membrane preparations were subjected to reactions with capsaicin and capsazepine at 0.5–250 μM, followed by measuring fluorescence polarization to determine the membrane interactivity to modify the fluidity of membranes. Both compounds acted on 1,2-dipalmitoylphosphatidylcholine bilayers and changed membrane fluidity. Capsaicin concentration-dependently interacted with neuro-mimetic membranes to increase their fluidity at low micromolar concentrations, whereas capsazepine inversely decreased the membrane fluidity. When used in combination, capsazepine inhibited the effect of capsaicin on neuro-mimetic membranes. In addition to the direct action on transmembrane ion channels, capsaicin and capsazepine share membrane interactivity, but capsazepine is likely to competitively antagonize capsaicin’s interaction with neuro-mimetic membranes at pharmacokinetically-relevant concentrations. The structure-specific membrane interactivity may be partly responsible for the analgesic effect of capsaicin.

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Section: Methodsmentioning

confidence: 99%