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

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Discussion
2003). Cholinergic muscarinic receptor subtypes are localized in special parts of
the body and are associated with numerous second messenger systems that
mediate a variety of pre- and postsynaptic responses (Dutar & Nicoll, 1989).
Central muscarinic M1 antagonism leads to cognitive dysfunction and other CNSrelated
adverse events. Muscarinic M1 and M2 knockout mice, both demonstrate
cognitive defects (Tzavara et al., 2003). In the central nervous system, most of the
cholinergic receptors are muscarinic. Muscarinic receptors exist pre- and
postsynaptically. Presynaptic receptors are involved in the regulation of ACh
release from the nerve terminals, while postsynaptic receptors are at the beginning
of the cascade of molecular events that will lead to the biological response. The
release of ACh from neurons in the central nervous system is modulated by
muscarinic agonists (Polak & Meeuws, 1966).
Cerebral cortex
Cerebral mAChR are involved in many physiological brain functions,
such as control of rapid eye movement, sleep (Velazquez-Moctezuma et al.,
1989), arousal (Albanus, 1970), learning and memory. Cerebral cortex participates
in the memory, attention, perceptual awareness, thought, language and
consciousness which are necessary for the normal life style. The muscarinic M1,
M3 and M5 receptors are located predominantly on postsynaptic nerve terminals
and are thought to be responsible for the role of the muscarinic cholinergic system
in cognition and long term potentiation in the hippocampus and cortex (Bartus,
2000). Immunoprecipitation and immunofluorescence studies indicate that
muscarinic M1 and M3 receptors are expressed in cortex (Levey, 1993).
Binding studies of total muscarinic and muscarinic M1 receptors revealed
decreased receptor number in the cerebral cortex during diabetic condition and in
hypoglycemic the expression was further decreased. Muscarinic M3 binding
significantly increased in hypoglycemic rats compared to diabetic. Real Time-
PCR analysis also revealed a down regulation of the muscarinic M1 receptor and