EP2 receptor stimulation promotes calcium responses in astrocytes via activation of the adenylyl cyclase pathway.
Astrocytes are a heterogeneous population of cells that are endowed with a great variety of receptors for neurotransmitters and neuromodulators. Recently prostaglandin E2 has attracted great interest since it is not only released by astrocytes but also activates receptors coupled to either phospholipase C or adenylyl cyclase. We report that EP2 receptor stimulation triggers cAMP production but also causes release of Ca2+ from intracellular stores. This effect is shared by other receptors similarly coupled to adenylyl cyclase and elicited by direct stimulation of the enzyme or application of cAMP analogues. However, the stimulation of the Ca2+ response by cAMP is not mediated by protein kinase A, since a specific antagonist of this kinase had no effect. Such a cross-talk between cAMP and Ca2+ was not observed in all astrocytes. It might therefore reflect a specific resource of either a subpopulation or astrocytes in a specific functional state.
Di Cesare
A
A
San Raffaele Scientific Institute, Milano, Italy.
Del Piccolo
P
P
Zacchetti
D
D
Grohovaz
F
F
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype
C482601:Epac protein, mouse; D020662:Guanine Nucleotide Exchange Factors; C545645:Ptger2 protein, mouse; C545646:Ptger2 protein, rat; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D015232:Dinoprostone