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Adenosine A 2B ‐receptor‐mediated cyclic AMP accumulation in primary rat astrocytes
Author(s) -
Peakman MarieClaire,
Hill Stephen J.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14043.x
Subject(s) - adenosine , adenosine receptor , neuroscience , astrocyte , chemistry , receptor , primary (astronomy) , adenosine a1 receptor , microbiology and biotechnology , endocrinology , pharmacology , biology , medicine , biochemistry , agonist , central nervous system , physics , astronomy
1 The effects of adenosine receptor agonists and antagonists on the accumulation of cyclic AMP have been investigated in primary cultures of rat astrocytes. 2 Adenosine A 2 ‐receptor stimulation caused a concentration‐dependent increase in the accumulation of [ 3 H]‐cyclic AMP in cells prelabelled with [ 3 H]‐adenine. The rank order of agonist potencies was 5′‐N‐ethylcarboxamidoadenosine (NECA; EC 50 = 1 μ m ) > adenosine (EC 50 = 5 μ m ) > 2‐chloroadenosine (EC 50 = 20 μ m ) >> CGS 21680 (EC 50 > 10 μ m ). The presence of 0.5 μ m dipyridamole, an adenosine uptake blocker, had no effect on the potency of adenosine. 3 The response to 10 μ m NECA was antagonized in a concentration‐dependent manner by the non‐selective adenosine receptor antagonists, xanthine amine congener (apparent K D = 12 nM), PD 115,199 (apparent K D = 134 nM) and 8‐phenyltheophylline (apparent K D = 126 nM). However, the A 1 ‐receptor‐selective antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine, had no significant effect on the responses to NECA or 2‐chloroadenosine at concentrations up to 1 μ m . 4 Stimulation of A 1 ‐receptors with the selective agonist, N 6 ‐cyclopentyladenosine, did not alter the basal accumulation of [ 3 H]‐cyclic AMP but inhibited a forskolin‐mediated elevation of [ 3 H]‐cyclic AMP accumulation by a maximal value of 42%. This inhibition was fully reversed in the presence of 0.1 μ m , 8‐cyclopentyl‐1,3‐dipropylxanthine. 5 The time course for NECA‐mediated [ 3 H]‐cyclic AMP accumulation was investigated. The results suggest that there is a substantial efflux of cyclic AMP from the cells in addition to the rapid and sustained elevation of intracellular cyclic AMP (5 fold over basal) which was also observed. 6 These data indicate that rat astrocytes in primary culture express an A 2B ‐adenosine receptor coupled positively to adenylyl cyclase. Furthermore, the presence of A 1 ‐receptors negatively coupled to adenylyl cyclase appears to have no significant effect on the A 2B ‐receptor‐mediated cyclic AMP responses to NECA and 2‐chloroadenosine.