Neurotransmitter-induced inositol phosphate formation in neurons in primary culture

Inositol-1,4,5-trisphosphate, produced in cells as a breakdown product of phosphatidylinositol-4,5-bisphosphate, induces, in many cell types, release of calcium from intracellular stores. In murine striatal neurons, differentiated in primary culture, carbachol, norepinephrine, glutamate, and neurotensin stimulate 3H-labeled inositol phosphate (3H-IP) production. The glutamate response was recently characterized as being mediated primarily by receptors of the quisqualate subtype. In the present study, we found that major differences exist between glutamate-stimulated 3H-IP formation and those stimulated by the other neuromediators. The maximal response to glutamate occurred before and during synaptogenesis and declined thereafter, whereas the maximal response to either carbachol or norepinephrine required complete neuronal differentiation. Although the glutamate response appears to be mediated exclusively by direct interaction with the neurotransmitter receptors, responses to carbachol, norepinephrine, and neurotensin were partially or completely blocked by tetrodotoxin.