Inhibition of cytochrome oxidase activity by local anaesthetics

Casanovas, Anna; Nebot, M.F. Malmary; Courrière, Philippe; Oustrin, J

doi:10.1016/0006-2952(83)90081-3

Cited by 18 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A variety of amine local anaesthetics (11 in all) with a significant range of lipophilicities (as measured by their octanol/water partition coefficients) demonstrated both competitive and mixed-type inhibition. Inhibition constants ranged from 40 mm for lidocaine (Casanovas et al, 1983) to 0.4 mm for dibucaine (Singer, 1982). It has been postulated both by Singer (1982) and by Casanovas et al (1985a,b) that the polar end of the anaesthetic molecule competes with substrate for binding whereas the non-polar end interacts with phospholipids bound to cytochrome c oxidase.…”

Section: Introductionmentioning

confidence: 99%

“…Cytochrome c oxidase has been previously used as a model for drug-membrane enzyme interactions (Singer, 1980(Singer, , 1982Chazotte & Vanderkooi, 1981;Vanderkooi & Chazotte, 1982;Casanovas et al, 1983Casanovas et al, , 1985a. A variety of amine local anaesthetics (11 in all) with a significant range of lipophilicities (as measured by their octanol/water partition coefficients) demonstrated both competitive and mixed-type inhibition.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The inhibition of a membrane-bound enzyme as a model for anaesthetic action and drug toxicity

Hasinoff

Davey

1989

Biochemical Journal

View full text Add to dashboard Cite

The inhibition of the membrane-bound enzyme cytochrome c oxidase by aliphatic n-alcohols and other neutral organic compounds was studied as a model for anaesthetic action and drug toxicity. The n-alcohols (C1 to C14) displayed a variation in inhibition constant of over 500,000-fold. The inhibition constants correlated well with the number of carbon atoms in the n-alcohols and also their n-octanol/water partition coefficients. General anaesthetic potency is known to be similarly well correlated with octanol/water partition coefficients. The free-energy change for transferring a methylene group of the n-alcohol to the more hydrophobic environment bound to the enzyme is similar to that for transferring a methylene group from water to pure alcohol. These results are consistent with the n-alcohols inhibiting by binding to an octanol-like environment on the enzyme or the protein/phospholipid interface. Neither negatively charged carboxylates nor positively charged amine analogues were observed to cause any inhibition, indicating that this postulated binding site may be uncharged. Inhibition of cytochrome c oxidase by n-alcohols was also demonstrated in both bovine heart and rat liver sonicated submitochondrial fragments.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The inhibition of a membrane-bound enzyme as a model for anaesthetic action and drug toxicity

Hasinoff

Davey

1989

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Apart from the alcohols investigated in this study and a previous study (Hasinoff & Davey, 1987), several other large organic compounds have also been observed to inhibit or bind to cytochrome c oxidase. A variety of hydrophobic amine local anaesthetics (11 in all) were observed to inhibit (Ki from 0.6 to 19 mM) cytochrome c oxidase (Singer, 1980;Casanovas et al, 1983). Quinacrine (Casanovas et al, 1985), six fully reduced flavin analogues (KdISS 5-8 /tM) (Ahmad et al, 1982) and galactosylsphingosine, which has a long hydrophobic tail (K1 approx.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study (Hasinoff & Davey, 1987) it was found that cytochrome c oxidase was inhibited at a hydrophobic binding site by a variety of alcohols. The presence of a hydrophobic inhibitor site has also been shown by the inhibition of cytochrome c oxidase by a number of hydrophobic amine local anaesthetics (Singer, 1980;Casanovas et al, 1983) and other compounds (Casanovas et al, 1985;Igisu & Nakamura, 1986). Likewise, adriamycin or its Fe3" complex might be capable of forming a complex with cytochrome c oxidase in a first step before inactivation of the enzyme.…”

Section: Introductionmentioning

confidence: 96%

The iron(III)-adriamycin complex inhibits cytochrome c oxidase before its inactivation

Hasinoff

Davey

1988

Biochemical Journal

View full text Add to dashboard Cite

Cytochrome c oxidase was found to be competitively inhibited by a complex formed between Fe3+ and the cardiotoxic antitumour drug adriamycin (doxorubicin) with an inhibition constant, Ki, of 12 microM. This competitive inhibition precedes the slower Fe3+-adriamycin induced inactivation of cytochrome c oxidase. In strong contrast with this result, free adriamycin was not observed to either inhibit or inactivate cytochrome c oxidase (Ki greater than 3 mM). Since, typically, polycations are known to inhibit cytochrome c oxidase, the competitive inhibition displayed by the Fe3+-adriamycin complex may also result from its polycationic character. Cytochrome c oxidase was also inhibited by pentan-1-ol (Ki 13 mM), and kinetic studies carried out in the presence of both inhibitors demonstrated that the Fe3+-adriamycin complex and pentan-1-ol are mutually exclusive inhibitors of cytochrome c oxidase. The inhibitor pentan-1-ol was also effective in preventing the slow inactivation of cytochrome c oxidase induced by Fe3+-adriamycin, presumably by blocking its binding to the enzyme. It is postulated that the slow inactivation of cytochrome c oxidase occurs when reactive radical species are produced while the Fe3+-adriamycin is complexed to cytochrome c oxidase in an enzyme-inhibitor complex. The Fe3+-adriamycin-induced inactivation of cytochrome c oxidase may be, in part, responsible for the cardiotoxicity of adriamycin.

show abstract

“…Therefore, another possible mechanism of cardioprotection is modulation of complex I protein by NO · -induced S-nitrosation leading to beneficial modulation of bioenergetics and redox signaling (Burwell et al, 2006). Complex IV is another target of NO · where it competes with O 2 at its binding site (Brookes et al, 2001); Similarly, VA were also reported to modulate complex IV activity and to alter its function (Casanovas et al, 1983; Szabo and Zoratti, 1993); however, whether this was through NO · was not evident. As noted earlier, in our recent study (Agarwal et al, 2014), we did not observe an effect of isoflurane on complex IV function.…”

Section: Other Potential Mitochondrial Targets Of Va During Ir Injurymentioning

confidence: 99%

Mitochondrial targets for volatile anesthetics against cardiac ischemia-reperfusion injury

et al. 2014

View full text Add to dashboard Cite

Mitochondria are critical modulators of cell function and are increasingly recognized as proximal sensors and effectors that ultimately determine the balance between cell survival and cell death. Volatile anesthetics (VA) are long known for their cardioprotective effects, as demonstrated by improved mitochondrial and cellular functions, and by reduced necrotic and apoptotic cell death during cardiac ischemia and reperfusion (IR) injury. The molecular mechanisms by which VA impart cardioprotection are still poorly understood. Because of the emerging role of mitochondria as therapeutic targets in diseases, including ischemic heart disease, it is important to know if VA-induced cytoprotective mechanisms are mediated at the mitochondrial level. In recent years, considerable evidence points to direct effects of VA on mitochondrial channel/transporter protein functions and electron transport chain (ETC) complexes as potential targets in mediating cardioprotection. This review furnishes an integrated overview of targets that VA impart on mitochondrial channels/transporters and ETC proteins that could provide a basis for cation regulation and homeostasis, mitochondrial bioenergetics, and reactive oxygen species (ROS) emission in redox signaling for cardiac cell protection during IR injury.

show abstract

Inhibition of cytochrome oxidase activity by local anaesthetics

Cited by 18 publications

References 14 publications

The inhibition of a membrane-bound enzyme as a model for anaesthetic action and drug toxicity

The inhibition of a membrane-bound enzyme as a model for anaesthetic action and drug toxicity

The iron(III)-adriamycin complex inhibits cytochrome c oxidase before its inactivation

Mitochondrial targets for volatile anesthetics against cardiac ischemia-reperfusion injury

Contact Info

Product

Resources

About