Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

detected readily in radioligand binding assays (Lazareno et al., 1990). Inhibition
of adenylyl cyclase activity by muscarinic agonists in rat corpus striatum is
mediated by M4 receptors (Caulfield, 1993; Olianas et al., 1996).
Muscarinic M5 receptor
The muscarinic M5 receptor was the last muscarinic acetylcholine
receptor cloned. Localisation studies have revealed that the M5R is abundantly
expressed in dopamine-containing neurons of the substantia nigra par compacta,
an area of the midbrain providing dopaminergic innervation to the striatum.
Concordantly, oxotremorine-mediated dopamine release in the striatum was
markedly decreased in M5R-deficient mice. More intriguingly, in M5R-deficient
mice, acetylcholine induced dilation of cerebral arteries and arterioles was greatly
attenuated (Yamada et al., 2001), suggesting that the M5 receptor is suitable target
for the treatment of cerebrovascular ischemia. Muscarinic M5 receptor subtype is
expressed at low levels in the brain (Hulme et al., 1990; Hosey, 1992).
Studies of the muscarinic M5 receptor have been hampered both by the
lack of selective ligands and of tissues or cell lines that endogenously express the
native receptor protein. Immunoprecipitation and RT-PCR studies have shown
that the M5 receptor is expressed at very low densities in the mammalian brain.
However, in situ hybridisation studies have demonstrated that M5 transcripts are
highly concentrated in the basal ganglia and are the only muscarinic receptor
transcripts expressed on dopaminergic neurons in the substantia nigra pars
compacta (SNc) and ventral tegmental area (VTA) (Reever et al., 1997). Another
potentially useful system is the eosinophilic leukemia cell line (EoL-1) where M5
receptors are induced on differentiation with interferon-γ (Mita et al., 1996).
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