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.
Balázs
R
R
Institute for Brain Aging and Dementia, University of California, Irvine 92697-4540, USA.
Miller
S
S
Chun
Y
Y
Cotman
C W
CW
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology*; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
D002614:Chelating Agents; C578937:Grm5 protein, rat; D010716:Phosphatidylinositols; D064529:Receptor, Metabotropic Glutamate 5; D011943:Receptors, Adrenergic, beta; D018094:Receptors, Metabotropic Glutamate; D004533:Egtazic Acid; D015759:Ionomycin; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium