The membrane concentrations of alcohol anesthetics

Seeman, Philip; Roth, Sheldon H.; Schneider, Henry

doi:10.1016/0005-2736(71)90210-0

Cited by 115 publications

(68 citation statements)

References 26 publications

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“…The results were calculated in terms of femtomoles of apomorphine specifically bound per mg of homogenate protein. Apomorphine is sufficiently hydrophobic and surface-active to warrant measuring the unbound (free) concentration (26)(27)(28) binding was defined as that amount bound in the presence of (-)-butaclamol minus that amount bound in the presence of (+)-butaclamol (7). The total [3H]apomorphine concentration was 1.6 nM (free concentration was 0.91 nM).…”

Section: Abstracimentioning

confidence: 99%

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Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.

Seeman¹,

Chau-Wong²,

Tedesco³

et al. 1976

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

133

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ABSTRACIIn order to develop a better dopamine receptor The homogenates from the human brain regions were prepared in the same way as those from the calf caudate, except that the preliminary crude homogenates of human brain were frozen in 1-ml aliquots, and after centrifugation they were resuspended in only 3 ml of buffer. Thus, the protein concentrations of both the human and calf homogenates were kept approximately equal. Optimum homogenization with the Polytron was obtained at a setting of 6 (for 20 sec) using a 16 X 100 mm glass test tube to hold the small 3-ml volume. Polytron settings greater than 6 (for 3 ml) caused a loss in binding sites; for calf homogenates, the optimum occurred at 7 (for 10 ml). (220), an aliquot of 0.5 ml was removed (polypropylene pipette tip) from the mixture and filtered under reduced pressure through a glass fiber filter (GF/B, Whatman, 24 mm diameter) using a Millipore stainless steel mesh support for the filter; the filtration took less than 1 sec. The filter was then washed twice with 5 ml of buffer per wash. The buffer was used at room temperature since minor differences in binding were found with the buffer at 40 or 37°. The wash buffer was delivered by gravity from a syringe Re-pipette over a period of 4 sec. The filters were not blotted or dried but placed directly into liquid scintillation vials; 8 ml of Aquasol (New England Nuclear Corp.) were added and the samples were monitored for 3H (25) after they were stored at 40 for at least 6 hr to allow temperature equilibration and to permit the glass fiber filters to become uniformly translucent. Specific binding of apomorphine was defined as that amount bound in the presence of 1 MM (-)-butaclamol minus that bound in the presence of 1 AM (+)-butaclamol, in accordance with previous work (7, 9) on dopamine receptors. The results were calculated in terms of femtomoles of apomorphine specifically bound per mg of homogenate protein. Apomorphine is sufficiently hydrophobic and surface-active to warrant measuring the unbound (free) concentration (26)(27)(28)

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Section: Abstracimentioning

confidence: 99%

mentioning

confidence: 99%

Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.

Seeman¹,

Chau-Wong²,

Tedesco³

et al. 1976

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

133

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show abstract

“…Two 0.5-ml aliquots of each supernatant were pipetted into liquid scintillation vials; Aquasol was added and the vials were monitored for 3H. The method for calculating the number of mol of drug adsorbed per mg of protein has been published (33).…”

mentioning

confidence: 99%

Brain receptors for antipsychotic drugs and dopamine: direct binding assays.

Seeman¹,

Chau-Wong²,

Tedesco³

et al. 1975

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

598

212

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“…(Nerve data for H(CH 2)n0H 3.0r The effects of various agents on the stability of the Nerve Dose erythrocyte membrane have been extensively studied FIGURE 3. Correlation between hemolytic activity and loss of nerve (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Hemolysis has been shown to correlate well with excitability induced by primary alcohols (n = 1 -9).…”

Section: Methodsmentioning

confidence: 99%

“…The relationship has been used to explain the potency of local anesthetics (4), general anesthetics (5), and tranquilizers and central nervous system depressants (6). The Meyer-Overton rule does not explain how the drug's lipid solubility leads to a disruption of membrane excitability, but many experimental observations are consistent with this view (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Hemolysis as a possible indicator of neurotoxicity induced by organic solvents.

Anderson¹,

Glasgow²,

Dunham³

1984

Environ Health Perspect

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The expense, length of time and number of animals required for routine toxicity testing have provided the incentive for finding alternative techniques which are faster, less expensive and equally valid. The purpose of this work was to examine the value of a simple in vitro test (hemolysis) as a correlate of the neurotoxicity produced by commonly used industrial organic solvents. Incubation of rat erythrocytes with organic alcohols produced hemolysis which correlates with the potency of the same alcohols to suppress membrane excitability, measured as reduction in the evoked action potential of the rat sciatic nerve. The hemolytic activity also reflects changes in water solubility among the compounds and thus can be used as an index of in vivo neurotoxicity, the extent of which partly depends on absorption of the agent and delivery to nerve tissue. Hemolysis therefore may be of value as a preliminary test for assessing the neurotoxicity of organic solvents.

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The membrane concentrations of alcohol anesthetics

Cited by 115 publications

References 26 publications

Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.

Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.

Brain receptors for antipsychotic drugs and dopamine: direct binding assays.

Hemolysis as a possible indicator of neurotoxicity induced by organic solvents.

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