Receptor-coupled phospholipase C and adenylyl cyclase function with different calcium pools in astrocytes

Astrocytes express phospholipase C (PLC)-coupled metabotropic glutamate receptors (only mGluR5 is detectable) and adenylyl cyclase (AC)-linked beta-adrenergic receptors. Calcium-sensitive effector enzymes are associated with these signal transduction pathways, but the relevant calcium compartments involved were found to be different. mGluR5-linked PLC responded primarily to extracellular Ca2+, suggesting a close spatial relation between the enzyme and Ca2+ entry channels. On the other hand, the calcium-inhibited AC associated with beta-adrenergic receptors was sensitive to intracellular Ca2+ selectively accessible to intracellular Ca2+ chelation. Furthermore, cAMP formation induced by direct activation of AC by forskolin was less responsive to intracellular Ca2+ chelation than that evoked by the receptor-activated AC, raising the possibility of selective access of the receptor to a pool of calcium-inhibited AC and/or the calcium modulation of some components of the coupling pathway.