The non-anaesthetic propofol analogue 2,6-di-tert-butylphenol fails to modulate GABA(A) receptor function.
Modulation of inhibitory synaptic transmission within the central nervous system contributes considerably to the anaesthetic effects of propofol and its analogues in vivo. We have studied the effects of the non-anaesthetic propofol analogue 2,6-di-tert-butylphenol on rat alpha(1)beta(2)gamma(2) GABA(A) receptors expressed in a mammalian expression system (HEK 293 cells) using the whole-cell patch clamp technique. Our experiments showed that 2,6-di-tert-butylphenol completely lacks co-activation and direct activation of the inhibitory GABA(A) receptor. Our results support the assumption that modulation of inhibitory GABA(A) receptor function is responsible for the anaesthetic effects of propofol in vivo.
Ahrens
Jörg
J
Department of Anaesthesiology, Hannover Medical School, Hannover, Germany. ahrens.j@mh-hannover.de
Leuwer
Martin
M
de la Roche
Jeanne
J
Foadi
Nilufar
N
Krampfl
Klaus
K
Haeseler
Gertrud
G
D018686:Anesthetics, Intravenous / Q000819:agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D058785:GABA-A Receptor Agonists; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000819:agonists / Q000494:pharmacology*; D015742:Propofol / Q000031:analogs & derivatives*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D058785:GABA-A Receptor Agonists; D010636:Phenols; D011963:Receptors, GABA-A; C035407:2,6-di-tert-butylphenol; D005680:gamma-Aminobutyric Acid; D015742:Propofol