Autoradiography of GABAa receptors

Ligand autoradiography, although usually lacking cellular resolution, serves as a highly-useful indicator of which apg2 subunit combination is present in a brain region (Korpi et al., 2002a) and is also a superbly quantitative technique (Korpi et al., 2002a). For example, the ligand [3H]flunitrazepam is incubated with a brain section in the absence or presence of the discriminating ligand CL 218 872. If the binding signal is reduced or even completely vanishes by co-incubation with CL 218 872 (which has high affinity for a1pg2

receptors and so displaces [3H]flunitrazepam), then this is a "BZ1 region''. If CL 218 872 fails to displace [3H]flunitrazepam, then this is a ''BZ2 -region'' (reviewed in Niddam et al., 1987). Thus BZ1-type binding marks a1pg2 receptors; 3H-zolpidem autoradiography on brain sections also selectively highlights a1pg2 receptors directly (Duncan et al., 1995; Korpi et al., 2002a). BZ2-type binding marks a2, a3 and a5pg2 type receptors (the a4pg2 receptors are not picked up by this method, as they do not bind [3H]flunitrazepam — see Section "GABAA receptors: allosteric modulation by benzodiazepines and related ligands''). The apg-type receptors with g1 or g3 are not picked up by BZ1 and BZ2 screening, neither are a4p8-type receptors. However, many novel ligands are available these days, which could be used as autoradiographic probes.

Autoradiography with [3H]muscimol (high-affinity site), commonly assumed to mark all GABAA receptors, selectively marks only a4p8 and a6p8 receptors; mouse brain sections with no 8 subunit no longer give detectable [3H]muscimol signals (Korpi et al., 2002b). Thus the [3H]muscimol autoradiographic signals detected in many basal ganglia areas such as the striatum (Olsen et al., 1990; Jones et al., 1997; Korpi et al., 2002b) will originate from a48 -containing receptors.

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