The anaesthetic steroid alphaxalone positively modulates alpha1-glycine receptor function.
Inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the processing of nociceptive signals, and mainly involves glycine. We have studied the effects of alphaxalone on alpha(1) homomeric glycine receptors expressed in a mammalian expression system (HEK 293 cells) using the whole-cell patch-clamp technique. Our experiments showed a coactivating effect of alphaxalone with a concentration for half-maximum activation (EC(50)) of the effect of a low glycine concentration (EC(20)) of 70.9 +/- 21.5 micromol/l. Taking into account the results of other groups, our study suggests that neuroactive steroids might be an interesting class of compounds to probe subunit-specific effects of glycine receptors.
Ahrens
Jörg
J
Department of Anaesthesiology, Hannover Medical School, Hannover, Germany. ahrens.j@mh-hannover.de
Leuwer
Martin
M
Demir
Reyhan
R
Krampfl
Klaus
K
Foadi
Nilufar
N
Haeseler
Gertrud
G
D000777:Anesthetics / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018408:Patch-Clamp Techniques; D011277:Pregnanediones / Q000008:administration & dosage / Q000494:pharmacology*; D021122:Protein Subunits; D018009:Receptors, Glycine / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000777:Anesthetics; D011277:Pregnanediones; D021122:Protein Subunits; D018009:Receptors, Glycine; C006477:alphaxalone