Fluorescence studies of drug and cation interactions with microsomal membranes

Hawkins, Hilary C.; Freedman, Robert B.

doi:10.1016/0014-5793(73)80127-9

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…The results also suggest that the presence of ionic sites in the membrane is important for the binding of lipid-soluble, charged compounds, and that such compounds exist, at least to some extent, in the ionized form in the membrane. These conclusions are supported by the results of Hawkins & Freedman (1973), who showed that (+)-benzphetamine and SKF-525A enhanced the fluorescence of ANS bound to microsomal membranes and, on the basis of pH studies, suggested that the enhancement was due to the protonated forms of the drugs.…”

Section: Discussionsupporting

confidence: 66%

“…The extrapolations were large and the intercepts on the ordinate small, so that no definite conclusions could be drawn. Hawkins & Freedman (1973) have previously drawn attention to these difficulties.…”

Section: Discussionmentioning

confidence: 99%

“…The binding of salts and drugs to biological membranes have also been investigated using fluorescent probes. Divalent cations and cationic drugs enhance the fluorescence of 1-anilino-8-naphthalene sulphonate (ANS) bound to various membranes (Gomperts, Lantelme & Stock, 1970;Rubalcava, de Mufioz & Gitler, 1969;Hawkins & Freedman, 1973;DiAugustine, Eling & Fouts, 1970;Wiethold et al, 1973). Drug-induced increases in the fluorescence of ANS have been correlated with changes in the structure of the erythrocyte membrane (Wiethold et al, 1973) and of the microsomal membranes of rat liver (DiAugustine et al, 1970).…”

Section: Introductionmentioning

confidence: 99%

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Interaction of Some Drugs, Metal Ions, and Alcohols With Rat Liver Microsomes as Studied With a Fluorescent Probe

Birkett

1974

Clin Exp Pharmacol Physiol

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S U M M A R Y 1. The effects of various compounds on the fluorescence of microsome-bound 1-anilino-8-naphthalene sulphonate (ANS) have been studied.2. Cationic drugs and divalent metal cations enhance the fluorescence of microsome-bound ANS whereas anionic drugs and primary aliphatic alcohols decrease it.3. No changes were observed in the fluorescence lifetime or emission maximum of ANS and it was concluded that there were no significant changes in the quantum yield of ANS fluorescence.4. The changes in fluorescence are shown to be related to changes in ANS binding.5. The results suggest that drug-induced changes in the binding of ANS to the microsomal membrane reflect a change in the net charge on the membrane as a result of the binding of a charged drug and that changes in ANS fluorescence cannot be directly interpreted as changes in the structure of the membrane.6 . Primary aliphatic alcohols displace ANS from the microsomal membrane but cause no change in quantum yield. It is suggested that the alcohols change the net charge on the membrane either by exposure of negative charges or occlusion of positive charges.7. The changes in ANS fluorescence can be used as a measure of the interaction of various drugs with the microsomal membrane. Apparent binding constants determined by this method for various drugs fall in the concentration ranges over which the drugs are reported to induce changes in membrane function in various in vitro systems.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interaction of Some Drugs, Metal Ions, and Alcohols With Rat Liver Microsomes as Studied With a Fluorescent Probe

Birkett

1974

Clin Exp Pharmacol Physiol

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“…Consistent with previous reports (Diaugustine et al, 1970;Hawkins and Freedman, 1973;Birkett, 1974), ANS fluorescence was enhanced by basic drugs that bound to HLMs, whereas acidic drugs and the neutral compound diazepam caused a decrease in ANS fluorescence. More importantly, there was a highly significant linear relationship between f u(mic) and the modulus of the fluorescence increment or decrement for the combined data set at each added drug concentration.…”

Section: Discussionsupporting

confidence: 92%

“…Thus, the binding of cations to phosphate and carboxyl groups, which decreases surface electrostatic potential, facilitates ANS binding and fluorescence (Slavik, 1982). Consistent with the known effects of membrane charge on ANS fluorescence, it has been demonstrated that several drugs that are positively charged at physiological pH enhance the fluorescence of microsome-bound ANS, whereas negatively charged drugs decrease the fluorescence of ANS in the presence of microsomes (Diaugustine et al, 1970;Hawkins and Freedman, 1973;Birkett, 1974). These data suggest that drug-induced shifts in baseline ANS fluorescence may provide a measure of the NSB of drugs to HLMs.…”

Section: Introductionsupporting

confidence: 59%