Anaesthesia makes up the largest hospital speciality and has a huge role to play in nearly every aspect of any hospital from operating theatres to accident and emergency, to the labour ward, and to intensive care. Our research ranges from basic molecular research into mechanisms of anaesthesia to investigating the clinical impact of novel anaesthetic agents.
Our research covers the entirety of patient’s perioperative journey and through this, we aim to deliver the greatest impact. The section has been pioneering in the development of novel technologies to facilitate the delivery of anaesthetic agents and has also made pivotal in-roads into the mechanism of action of anaesthetic agents and their wider application to other diseases (such as their protective roles in brain injury and in cancer).
@article{Yip:2013:10.1038/nchembio.1340,
author = {Yip, GM and Chen, ZW and Edge, CJ and Smith, EH and Dickinson, R and Hohenester, E and Townsend, RR and Fuchs, K and Sieghart, W and Evers, AS and Franks, NP},
doi = {10.1038/nchembio.1340},
journal = {Nature Chemical Biology},
pages = {715--720},
title = {A propofol binding site on mammalian GABAA receptors identified by photolabeling},
url = {http://dx.doi.org/10.1038/nchembio.1340},
volume = {9},
year = {2013}
}
TY - JOUR
AB - Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABAA (γ-aminobutyric acid type A) receptors, but where it binds to this receptor is not known and has been a matter of some debate. We synthesized a new propofol analog photolabeling reagent whose biological activity is very similar to that of propofol. We confirmed that this reagent labeled known propofol binding sites in human serum albumin that have been identified using X-ray crystallography. Using a combination of protiated and deuterated versions of the reagent to label mammalian receptors in intact membranes, we identified a new binding site for propofol in GABAA receptors consisting of both β3 homopentamers and α1β3 heteropentamers. The binding site is located within the β subunit at the interface between the transmembrane domains and the extracellular domain and lies close to known determinants of anesthetic sensitivity in the transmembrane segments TM1 and TM2.
AU - Yip,GM
AU - Chen,ZW
AU - Edge,CJ
AU - Smith,EH
AU - Dickinson,R
AU - Hohenester,E
AU - Townsend,RR
AU - Fuchs,K
AU - Sieghart,W
AU - Evers,AS
AU - Franks,NP
DO - 10.1038/nchembio.1340
EP - 720
PY - 2013///
SN - 1552-4469
SP - 715
TI - A propofol binding site on mammalian GABAA receptors identified by photolabeling
T2 - Nature Chemical Biology
UR - http://dx.doi.org/10.1038/nchembio.1340
UR - http://hdl.handle.net/10044/1/32933
VL - 9
ER -