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

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Discussion
hypoglycemic and diabetic rats to know whether the observed cholinergic and
GABAergic neurotransmitter changes at receptor level induced by hypoglycemia
and hyperglycemia is modulated at second messenger level. Results showed a
decreased expression of phospholipase C in the cerebral cortex, cerebellum, brain
stem, corpus striatum and hippocampus of hypoglycemic rats compared to
diabetic- hyperglycemic and control rats.
Muscarinic M1, M3, M5 receptors typically couple via α subunits of the
Gq/11 family to activate phospholipase C, stimulating phosphoinositide (PI)
hydrolysis (Caulfield & Birdsall, 1998). In particular, reconstitution experiments
with purified muscarinic M1 receptors, G protein subunits, and PLC suggested
that the β1 subtype of PLC serves as the primary effector for the muscarinic M1
receptor (Jose et al., 1995). We considered that the down regulation of the
Phospholipase C in rat brain regions during hypoglycemia contribute to the
impaired signal transduction of G-protein coupled neurotransmitter receptors.
Altered phospholipase C expression fails to modulate the activity of downstream
proteins important for cellular signaling. Defective expression of phospholipase C
results in low levels of IP3 causing the impaired release of Ca 2+ and bring down
the level of intracellular calcium and thus failed to execute the normal neuronal
function in brain regions. Previous studies reported that phospholipase C mediated
signaling, initiated by growth factor receptor types, are involved in long-term
memory formation, a process that requires gene expression (Paul et al., 2008).
Reports also showed that under abnormal conditions, excessive
phospholipase activation, along with a decreased ability to resynthesize membrane
phospholipids, lead to the generation of free radicals, excitotoxicity, mitochondrial
dysfunction and apoptosis/necrosis.
Pancreas
The physiologic regulation of insulin secretion from the pancreatic β cell
is dependent upon the coordinated interaction of metabolic and neurohumoral