Potentiated cAMP rise in metabotropically stimulated rat cultured astrocytes by a Ca2+-related A1/A2 adenosine receptor cooperation.
Adenosine agonists favoured an intracellular Ca2+ rise in cultured type 1 astrocytes if the metabotropic glutamate receptors were concomitantly stimulated by (2S, 1's, 2's)-2-(carboxycyclopropyl)glycine (L-CCG-I; group II agonist), quisqualate (group I agonist) or 1-aminocyclopentane-trans-1, 3-dicarboxylic acid (t-ACPD; groupI/II agonist). Since the generation of a Ca2+ signal reflected a newly adopted adenosine A1 receptor action, we tested the possible consequence that the established opposing control of the cellular cAMP content by inhibitory A1 and stimulatory A2 receptor activation was also altered. During metabotropic receptor stimulation by LCCG-I, quisqualate or t-ACPD, the non-selective adenosine agonist 2-chloroadenosine (Cl-adenosine) caused a potentiated cAMP increase which markedly exceeded that produced by Cl-adenosine alone. This cAMP potentiation resulted from altered and Ca2+-dependent A1/A2 receptor cooperation. It was abolished by A1 receptor blockade and could not be achieved in the presence of t-ACPD by the A1 agonist R(-)N6-(2-phenylisopropyl)-adenosine or by the A2 agonist 5'-N-ethyl carboxyamidoadenosine alone, but obtained using their combination. The cAMP potentiation was blocked by intracellular Ca2+ chelation and the required A1 receptor action could be mimicked by a Ca2+ signal generated by the P2y receptor agonist adenosine 5'-(beta-thio)diphosphate. The results support the conclusion that nanomolar concentrations of adenosine may influence astrocyte reactions by stimulating Ca2+ and cAMP-dependent signalling cascade.
Ogata
T
T
Max Planck Institute for Psychiatry, Department of Neuromorphology, am Klopferspitz 18a, 82152 Martinsried, Germany.
Nakamura
Y
Y
Schubert
P
P
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013268:Stimulation, Chemical
D000600:Amino Acids, Dicarboxylic; D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D058906:Purinergic P1 Receptor Agonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C035261:(alpha-carboxycyclopropyl)glycine; D016318:Quisqualic Acid; D000242:Cyclic AMP; C012729:2-amino-4-phosphonobutyric acid; D002118:Calcium