Mitochondria uncoupling effect of halothane dependent on magnesium

Rzeczycki, W; Valdivia, Enrique

doi:10.1016/0006-291x(73)90983-2

Biochemical and Biophysical Research Communications

1973

DOI: 10.1016/0006-291x(73)90983-2

|View full text |Cite

Mitochondria uncoupling effect of halothane dependent on magnesium

W Rzeczycki

Enrique Valdivia

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1973

1991

Publication Types

Select...

Article6

Relationship

Self Cite0

Independent6

Authors

Journals

Cited by 6 publications

(1 citation statement)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of particular interest are the general anesthetics, which are similar to protonophoric uncouplers in their effect on succinate respiration and on ATP synthesis and hydrolysis in mitochondria. Earlier studies, mostly with halothane, indicated that general anesthetics inhibit NADH respiration and uncouple succinate respiration, but they did not resolve the mechanism by which anesthetics affect mitochondria (5)(6)(7)(8)(9). General anesthetics are not expected to be protonophores, per se, but might affect proton transport or other ion transport indirectly, leading to the collapse of ASH (8)(9)(10).…”

mentioning

confidence: 99%

Uncoupling of oxidative phosphorylation in rat liver mitochondria by general anesthetics.

Rottenberg¹

1983

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

The general anesthetics chloroform and halothane inhibit ATP synthesis in rat liver mitochondria, in the millimolar concentration range (1-12 mM), in parallel with a reduction of respiratory control and the ratio of ATP produced to oxygen consumed. In these effects, halothane and chloroform are similar to classical, protonophoric, uncouplers. The rate of ADP-stimulated respiration or the rate of uncoupler-stimulated respiration is not affected. Like classical uncouplers, halothane and chloroform also stimulate mitochondrial ATPase activity. However, the extent of stimulation by these agents is larger than by protonophoric uncouplers and, more significantly, ATPase activity stimulated by carbonylcyanide m-chlorophenylhydrazone is further stimulated by these agents. In the presence of the Ca2+ chelator EGTA, halothane and chloroform have no measurable effect on the magnitude of the proton electrochemical potential, A!H. In the absence of EGTA these anesthetics have a small effect on AAH, apparently due to stimulation of Ca2+ cycling. Under these conditions the membrane potential is decreased while ApH is increased, but the total value of AIAH is only slightly decreased. The uncoupling activity of the anesthetics is the same in the presence or absence of EGTA. Thus, in contrast to protonophoric uncouplers, the uncoupling effect of general anesthetics does not depend on the collapse of AAH. In the same concentration range in which anesthetics uncouple oxidative phosphorylation both halothane and chloroform increase membrane fluidity, as measured by the partitioning of the hydrophobic spin probe 5-doxyldecane. These findings suggest a role for intramembrane processes in energy conversion that is not dependent on the bulkl AAH.Oxidative phosphorylation in mitochondria is believed to be mediated by the proton electrochemical potential gradient (ASH) as postulated by Mitchell in the chemiosmotic hypothesis (1-3). According to the chemiosmotic scheme, uncouplers are protonophores that catalyze the transport of protons across the membrane, thereby collapsing AAH, which is the direct driving force for ATP synthesis. The evidence for the protonophoric activity of uncouplers in both natural membranes and phospholipid bilayers is overwhelming (for review see ref. 4). In mitochondria, where ApH is relatively small, the collapse of membrane potential by electrophoretic transport of cations (e.g., Ca2" or K+ in the presence of valinomycin) is sufficient to decrease ASH and lead to uncoupling as well. Thus, to date, all known uncouplers of oxidative phosphorylation and photophosphorylation appear to collapse AAH in correlation with the inhibition of ATP synthesis (but see Discussion). However, several agents whose mechanism of action is still unknown are known to inhibit oxidative phosphorylation. Of particular interest are the general anesthetics, which are similar to protonophoric uncouplers in their effect on succinate respiration and on ATP synthesis and hydrolysis in mitochondria. Earlier studies, mostly with hal...

show abstract

mentioning

confidence: 99%

Uncoupling of oxidative phosphorylation in rat liver mitochondria by general anesthetics.

Rottenberg¹

1983

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

show abstract

Initiation of free radical reactions and hepatotoxicity in rats poisoned with carbon tetrachloride or bromotrichloromethane

et al. 1973

View full text Add to dashboard Cite

Morphological studies [1, 2] have shown that bromotrichloromethane behaves as a more dangerous hepatotoxin than carbon tetrachloride.The present investigation extends those preliminary findings and offers new biochemical evidences for the hypothesis suggested by the relationship between the toxicity and the level of the bond dissociation energy. The electron paramagnetic resonance signal and the UVspectrum of double bond shifting in microsomal lipids show that CBrCI3 administration induces a more rapid and extensive free radical reaction in liver than CCI 4. More severe pathological phenomena are coincident with a more profound pro-oxidant effect of bromotrichloromethane. In fact, 0.26 mmol of CBrC13 prove lethal after having caused massive fatty liver and necrosis, while an equimolecular amount of CCI~ induces a lower and transient hepatic triglyceride accumulation and necrosis. Under the same experimental conditions, the lethal dose of carbon tetrachloride is twenty times higher (5.16 mmol per 100 g body weight). CCl4-poisoned rats develop a remarkable dissociation of liver polysomes. In animals given an equivalent dose of CBrCI~ these damages occur within a shorter lag period and are more severe. Moreover, the recovery takes place much later than when carbon tetrachloride is used.A clear inverse relationship exists between the level of bond dissociation energy of these two halogenoalkanes (respectively, 49 and 68 kcal tool -1, for CBrC13 and CCIa) and their potency to stimulate free radical reactions and to produce liver injury.

show abstract

Effect of 1,1,1-trichloroethane on mitochondrial metabolism

Herd

Martin

1975

Biochemical Pharmacology

View full text Add to dashboard Cite

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Mitochondria uncoupling effect of halothane dependent on magnesium

Cited by 6 publications

References 8 publications

Uncoupling of oxidative phosphorylation in rat liver mitochondria by general anesthetics.

Uncoupling of oxidative phosphorylation in rat liver mitochondria by general anesthetics.

Initiation of free radical reactions and hepatotoxicity in rats poisoned with carbon tetrachloride or bromotrichloromethane

Effect of 1,1,1-trichloroethane on mitochondrial metabolism

Contact Info

Product

Resources

About