Shine and Rise
In a new study, a light-sensitive moiety has been added to propofol, a
commonly used anesthetic, allowing its narcotic effect to be controlled by
light. The compound also offers a possible route to the treatment of certain
eye diseases.
Inhibitory neurotransmitters dampen the activity of neurons. This regulatory
effect forms the basis for the action of many anesthetics. For example,
propofol, a common anesthetic, interacts with receptors on neural cell
membranes that normally bind the inhibitory neurotransmitter gamma-amino
butyric acid (GABA). Binding of GABA opens protein channels through which
negatively charged chloride ions stream into the cell. By raising the resting
electrical potential across the membrane, this makes the cell less likely to
fire in response to an incoming stimulus. Propofol magnifies this effect and
this functions as an anesthetic.
Dirk Trauner, Professor of Chemical Biology and Genetics at LMU and a member
of the Excellence Cluster CIPSM, is a specialist in the art of conferring on
"blind" nerve cells the ability to react to light. Working with colleagues
based in Switzerland and the US, he has now developed a derivative of
propofol that allows the action of the GABA receptor to be regulated by
light. "By attaching a molecular switch to propofol, we have obtained a
light-sensitive molecule that is a more potent anesthetic than propofol
itself, in the dark," Trauner explains.
Sleepless when the sun shines
In this case, light serves to largely inactivate the anesthetic effect of the
compound, as the researchers were able to demonstrate in experiments on
tadpoles. When exposed to a low concentration of the propofol derivative, the
animals were anesthetized, as expected. However, when irradiated with violet
light, they promptly revived, but remained active only as long as the light
was on. In the dark, they were immobilized once again. The light-dependent
effect is completely reversible, as the tadpoles recovered fully upon
transfer to their normal aquarium.
The new agent could be used to treat certain forms of blindness, such as
retinitis pigmentosa, which leads to loss of vision owing to progressive
destruction of photoreceptors. However, neurons deeper in the retina are
unaffected, and are accessible to ambient light. "The inner cells also bear
GABA receptors on their surfaces, and in principle they could be turned into
light-responsive cells with the help of the new compound, which would allow
us to bypass the defective photoreceptors," says Trauner. He and his research
group are now actively exploring this possibility. (Angewandte Chemie, 13.
September 2012) göd
In a new study, a light-sensitive moiety has been added to propofol, a
commonly used anesthetic, allowing its narcotic effect to be controlled by
light. The compound also offers a possible route to the treatment of certain
eye diseases.
Inhibitory neurotransmitters dampen the activity of neurons. This regulatory
effect forms the basis for the action of many anesthetics. For example,
propofol, a common anesthetic, interacts with receptors on neural cell
membranes that normally bind the inhibitory neurotransmitter gamma-amino
butyric acid (GABA). Binding of GABA opens protein channels through which
negatively charged chloride ions stream into the cell. By raising the resting
electrical potential across the membrane, this makes the cell less likely to
fire in response to an incoming stimulus. Propofol magnifies this effect and
this functions as an anesthetic.
Dirk Trauner, Professor of Chemical Biology and Genetics at LMU and a member
of the Excellence Cluster CIPSM, is a specialist in the art of conferring on
"blind" nerve cells the ability to react to light. Working with colleagues
based in Switzerland and the US, he has now developed a derivative of
propofol that allows the action of the GABA receptor to be regulated by
light. "By attaching a molecular switch to propofol, we have obtained a
light-sensitive molecule that is a more potent anesthetic than propofol
itself, in the dark," Trauner explains.
Sleepless when the sun shines
In this case, light serves to largely inactivate the anesthetic effect of the
compound, as the researchers were able to demonstrate in experiments on
tadpoles. When exposed to a low concentration of the propofol derivative, the
animals were anesthetized, as expected. However, when irradiated with violet
light, they promptly revived, but remained active only as long as the light
was on. In the dark, they were immobilized once again. The light-dependent
effect is completely reversible, as the tadpoles recovered fully upon
transfer to their normal aquarium.
The new agent could be used to treat certain forms of blindness, such as
retinitis pigmentosa, which leads to loss of vision owing to progressive
destruction of photoreceptors. However, neurons deeper in the retina are
unaffected, and are accessible to ambient light. "The inner cells also bear
GABA receptors on their surfaces, and in principle they could be turned into
light-responsive cells with the help of the new compound, which would allow
us to bypass the defective photoreceptors," says Trauner. He and his research
group are now actively exploring this possibility. (Angewandte Chemie, 13.
September 2012) göd
