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Potentiated cAMP Rise in Metabotropically Stimulated Rat Cultured Astrocytes by a Ca 2+ ‐related A l /k 2 Adenosine Receptor Cooperation
Author(s) -
Ogata Tadanori,
Nakamura Yoichi,
Schubert Peter
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01280.x
Subject(s) - agonist , adenosine , metabotropic receptor , adenosine receptor , medicine , metabotropic glutamate receptor , endocrinology , adenosine a1 receptor , receptor , adenosine a2b receptor , chemistry , biology
Adenosine agonists favoured an intracellular Ca 2+ rise in cultured type 1 astrocytes if the metabotropic glutamate receptors were concomitantly stimulated by (2 S ,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; group VII agonist). Since the generation of a Ca 2+ signal reflected a newly adopted adenosine A 1 receptor action, we tested the possible consequence that the established opposing control of the cellular cAMP content by inhibitory A 1 and stimulatory A 2 receptor activation was also altered. During metabotropic receptor stimulation by L‐CCG‐I, quisqualate or t ‐ACPD, the non‐selective adenosine agonist 2‐chloroadenosine (CI‐adenosine) caused a potentiated cAMP increase which markedly exceeded that produced by CI‐adenosine alone. This cAMP potentiation resulted from altered and Ca 2+ ‐dependent A 1 /A 2 receptor cooperation. It was abolished by A 1 receptor blockade and could not be achieved in the presence of t ‐ACPD by the A 1 agonist R(‐) N 6 ‐(2‐phenylisopropyl)‐adenosine or by the A 2 agonist 5′‐ N ‐ethyl carboxyamidoadenosine alone, but was obtained using their combination. The cAMP potentiation was blocked by intracellular Ca 2+ chelation and the required A 1 receptor action could be mimicked by a Ca 2+ signal generated by the P 2y receptor agonist adenosine 5β‐(β‐thio) diphosphate. The results support the conclusion that nanomolar concentrations of adenosine may influence astrocyte reactions by stimulating the Ca 2+ and cAMP‐dependent signalling cascade.