A Human TREK-1/HEK Cell Line: A Highly Efficient Screening Tool for Drug Development in Neurological Diseases

TREK-1 potassium channels are involved in a number of physiopathological processes such as neuroprotection, pain and depression. Molecules able to open or to block these channels can be clinically important. Having a cell model for screening such molecules is of particular interest. Here, we describe the development of the first available cell line that constituvely expresses the TREK-1 channel. The TREK-1 channel expressed by the h-TREK-1/HEK cell line has conserved all its modulation properties. It is opened by stretch, pH, polyunsaturated fatty acids and by the neuroprotective molecule, riluzole and it is blocked by spadin or fluoxetine. We also demonstrate that the h-TREK-1/HEK cell line is protected against ischemia by using the oxygen-glucose deprivation model

The mechanism of action of zopiclone

SummaryThe mechanism of action of the cyclopyrrolone hypnotic drug zopiclone involves allosteric modulation of the GABAAreceptor. Zopiclone displaces the binding of [3H]-flunitrazepam with an affinity of 28 nM, and enhances the binding of the channel blocker [35S]-TBPS. The binding of zopiclone, unlike that of hypnotic benzodiazepines, is not facilitated by GABA. Zopiclone does not distinguish between GABAA receptors containing different α-subunits (BZ1and BZ2phenotype). Studies with protein-modifying agents (egdiethylpyrocarbonate) and photoaffinity labelling suggest that cyclopyrrolones bind to a domain on the GABAA receptor different from the benzodiazepine binding domain. The consequence of this interaction with the GABAAreceptor is to potentiate responses to GABA, as can be demonstrated by electrophysiological methods. Subchronic treatment of mice with high doses of zopiclone does not produce the changes in sensitivity of the GABAAreceptor that are observed with hypnotic benzodiazepines.</jats:p

In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: A film and electronic autoradiographic study

To further validate its use in positron emission tomography (PET), we studied the binding of [18F]altanserin, a specific 5HT2 radioligand, in the rat brain using in vivo autoradiography. Distribution of [18F]altanserin binding was comparable to the in vitro mapping of 5HT2 receptors reported in the literature. Selective displacers were used to test the reversibility and the selectivity of this radioligand. Specific binding of [18sF]altanserin in the rat frontal cortex was quantified by direct counting with an electronic imaging system and by quantification on digitalized autoradiograms. Close results of about 30 pmol/g were obtained with both methods. Our data confirmed that [18F]altanserin is a valid tracer for 5HT2 receptors binding studies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe