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

GABA limit excitation and prevent this excitation from reaching neurotoxic
levels. Activation of GABAA receptors increases C1 - conductance, inducing
hyperpolarization and reducing cell excitability (Sivilotti & Nistri, 1991).
Enhanced GABA release increases extracellular GABA levels, thus contributing
to the maintenance of homeostasis in the hippocampus upon impending
hyperexcitation. Moreover, hippocampal GABAergic neurons are more resistant
than excitatory aminoacid neurons to transient ischemia (Matsumoto et al., 1991).
The augmentation of inhibitory mechanisms has important neuroprotective effects.
To date, drugs that enhance GABAergic systems provide significant neuronal
protection when used before or after insults. Thus, any impairment in the
GABAergic mechanism in the CNS and/or in the PNS is important in the
pathogenesis of hypoglycemia and diabetes.
Insulin and Insulin receptors in the brain
Two decades ago both insulin and its receptors were discovered in the
brain (Havrankova et al., 1978). Moreover, contrary to old assumptions, it is now
known that insulin is actively transported across the blood–brain barrier and it is
produced locally in the brain (Schwartz et al., 1998). Concentrations of insulin
receptors in the brain are particularly high in neurons, with abundant insulin
receptor protein in both cell bodies and synapses (Zhao et al., 1999).
These findings have raised questions about the physiological role of
insulin in the brain. Some suggest that, as in peripheral tissues, insulin mainly acts
by mediating cerebral glucose uptake (Hoyer, 1998), but this opinion is not shared
by others. Insulin and insulin receptors appear to play a modulatory role in certain
behaviours, such as feeding behaviour, learning and memory (Wickelgren, 1998;
Kumagai , 1999). For example, after training in a water maze, insulin receptor
mRNA levels were increased in the hippocampus of rats, in parallel with
accumulation of insulin receptor protein. Moreover, intracerebroventricular
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