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Adenosine A 1 receptor‐mediated changes in basal and histamine‐stimulated levels of intracellular calcium in primary rat astrocytes
Author(s) -
Peakman MarieClaire,
Hill Stephen J.
Publication year - 1995
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.1476-5381.1995.tb15004.x
Subject(s) - histamine , calcium , medicine , endocrinology , extracellular , adenosine , calcium in biology , agonist , basal (medicine) , astrocyte , biology , histamine receptor , stimulation , histamine h1 receptor , receptor , chemistry , biochemistry , central nervous system , antagonist , insulin
1 The effects of adenosine A 1 receptor stimulation on basal and histamine‐stimulated levels of intracellular free calcium ion concentration ([Ca 2+ ] i ) have been investigated in primary astrocyte cultures derived from neonatal rat forebrains. 2 Histamine (0.1 μ m ‐l mM) caused rapid, concentration‐dependent increases in [Ca 2+ ] i over basal levels in single type‐2 astrocytes in the presence of extracellular calcium. A maximum mean increase of 1,468 ±94 nM over basal levels was recorded in 90% of type‐2 cells treated with 1 mM histamine ( n = 49). The percentage of type‐2 cells exhibiting calcium increases in response to histamine appeared to vary in a concentration‐dependent manner. However, the application of 1 mM histamine to type‐1 astrocytes had less effect, eliciting a mean increase in [Ca 2+ ] i of 805 ± 197 nM over basal levels in only 30% of the cells observed ( n = 24). 3 In the presence of extracellular calcium, the A 1 receptor‐selective agonist, N 6 ‐cyclopentyladenosine (CPA, 10 μ m ), caused a maximum mean increase in [Ca 2+ ] i of 1,110 ± 181 nM over basal levels in 30% of type‐2 astrocytes observed ( n = 53). The size of this response was concentration‐dependent; however, the percentage of type‐2 cells exhibiting calcium increases in response to CPA did not appear to vary in a concentration‐dependent manner. A mean calcium increase of 605 ± 89 nM over basal levels was also recorded in 23% of type‐1 astrocytes treated with 10 μ m CPA ( n = 30). 4 In the absence of extracellular calcium, in medium containing 0.1 mM EGTA, a mean increase in [Ca 2+ ] i of 504 ±67 nM over basal levels was recorded in 41% of type‐2 astrocytes observed ( n = 41) after stimulation with 1 μ m CPA. However, in the presence of extracellular calcium, pretreatment with the A 1 receptor‐selective antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine, for 5–10 min before stimulation with 1 μ m CPA, completely antagonized the response in 100% of the cells observed. 5 In type‐2 astrocytes, prestimulation with 10 nM CPA significantly increased the size of the calcium response produced by 0.1 μ m histamine and the percentage of responding cells. Treatment with 0.1 μ m histamine alone caused a mean calcium increase of 268 ±34 nM in 41% of the cells observed ( n = 34). After treatment with 10 nM CPA, mean calcium increase of 543 ±97 nM was recorded in 100% of the cells observed ( n = 33). 6 These data indicate that adenosine A 1 receptors couple to intracellular calcium mobilization and extracellular calcium influx in type‐1 and type‐2 astrocytes in primary culture. In addition, the simultaneous activation of adenosine A 1 receptors on type‐2 astrocytes results in an augmentation of the calcium response to histamine H 1 receptor stimulation.