Abstract
To investigate changes in muscarinic receptor‐stimulated phospholipase C‐β (PLC‐β) activity during brain development, we examined the functional coupling of each of the three major protein components of the phosphoinositide system (M~1~, M~3~, and M~5~ muscarinic receptor subtypes; G~q/11~ proteins; PLC‐β~1–4~ isoforms) in membrane preparations from post‐mortem human prefrontal cerebral cortex collected at several stages of prenatal and postnatal development. In human prenatal brain membranes, PLC was found to be present and could be activated by calcium, but the ability of guanosine‐5′‐o‐3 thiotriphosphate (GTPγS) or carbachol (in the presence of GTPγS) to modulate prenatal PLC‐β was significantly weaker than that associated with postnatal PLC‐β. Western blot analysis revealed that the levels of Gα~q/11~ did not change significantly during development. In contrast, dramatically higher levels of expression of PLC‐β~1–4~ isoforms and of M~1~, M~3~, and M~5~ muscarinic receptors were detected in the child vs. the fetal brain, a finding that might underlie the observed increased activity of PLC. Thus, inositol phosphate production may be more efficiently regulated by altering the amount of effectors (PLC‐β~1–4~) and receptors (M~1,3,5~ subtypes) than by altering the level of Gα~q/11~ subunits. These results demonstrate that different PLC isoforms are expressed in the prefrontal cortex of the developing human brain in an age‐specific manner, suggesting specific roles not only in synaptic transmission but also in the differentiation and maturation of neurons in the developing brain. © 2006 Wiley‐Liss, Inc.