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A Novel Effect of Cyclic AMP on Capacitative Ca 2+ Entry in Cultured Rat Cerebellar Astrocytes
Author(s) -
Lin Wu Mei,
Chen WeiHao,
Liu I.Hsiu,
Tseng ChuenDen,
Wang SeuMei
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731318.x
Subject(s) - forskolin , protein kinase c , second messenger system , intracellular , endoplasmic reticulum , protein kinase a , medicine , endocrinology , cyclic adenosine monophosphate , adenosine , calcium , biology , astrocyte , calcium in biology , chemistry , microbiology and biotechnology , biochemistry , signal transduction , kinase , receptor , central nervous system , stimulation
: One of the most important intracellular Ca 2+ regulatory mechanisms in nonexcitable cells, “capacitative Ca 2+ entry” (CCE), has not been adequately studied in astrocytes. We therefore investigated whether CCE exists in cultured rat cerebellar astrocytes and studied the roles of cyclic AMP (cAMP) and protein kinase C (PKC) in CCE. We found that (1) at least two different intracellular Ca 2+ stores, the endoplasmic reticulum and mitochondria, are present in cerebellar astrocytes ; (2) CCE does exist in these cells and can be inhibited by Ni 2+ , miconazole, and SKF 96365 ; (3) CCE can be directly enhanced by an increase in intracellular cAMP, as 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐brcAMP), forskolin, and isobutylmethylxanthine have stimulatory effects on CCE ; and (4) neither of the two potent protein kinase A (PKA) inhibitors, H8 and H89, nor a specific PKA agonist, Sp ‐adenosine 3′,5′‐cyclic monophosphothioate, had a significant effect on cAMP‐enhanced Ca 2+ entry. The [Ca 2+ ] i increase was not due to a release from calcium stores, hyperpolarization of the membrane potential, inhibition of calcium extrusion, or a change in pH i , suggesting that cAMP itself probably acts as a novel messenger to modulate CCE. We also conclude that activation of PKC results in an increase in CCE. cAMP and PKC seem to modulate CCE by different pathways.