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Opposite Regulation of Adenylyl Cyclase by Protein Kinase C in Astrocyte and Microglia Cultures
Author(s) -
Patrizio Mario,
Slepko Natalia,
Levi Giulio
Publication year - 1997
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.1471-4159.1997.69031267.x
Subject(s) - calphostin c , adenylyl cyclase , protein kinase c , adcy9 , adcy10 , forskolin , staurosporine , camp dependent pathway , protein kinase a , astrocyte , adcy6 , biology , phosphodiesterase , endocrinology , chemistry , medicine , microbiology and biotechnology , signal transduction , biochemistry , receptor , kinase , central nervous system , enzyme
We studied the regulation of cyclic AMP responses by protein kinase C (PKC) in purified astrocyte and microglia cultures obtained from the neonatal rat brain. In astrocytes, a 10‐min treatment with the phorbol esters phorbol 12‐myristate 13‐acetate (PMA) and 4β‐phorbol 12,13‐didecanoate (4β‐PDD) (but not with 4α‐PDD) or with diacylglycerol, which activate PKC, dose‐dependently enhanced cyclic AMP accumulation induced by the β‐adrenergic agonist isoproterenol and the adenylyl cyclase activator forskolin. Such enhancement was prevented by the PKC inhibitors staurosporine and calphostin‐C and by down‐regulation of PKC and was not related to activation of membrane receptors or G s proteins or to inhibition of G i proteins or phosphodiesterases. Instead, the activity of adenylyl cyclase doubled in PMA‐treated astrocytes. In microglia, a 10‐min treatment with PMA or PKC inhibitors did not affect cyclic AMP accumulation, whereas longer treatments with PMA or 4β‐PDD (but not 4α‐PDD) inhibited the cyclic AMP response in a time‐ and dose‐dependent manner. Such inhibition was mimicked by staurosporine and calphostin‐C. Also, in the case of microglia, the modulation of cyclic AMP responses appeared to occur at the level of adenylyl cyclase, and not elsewhere in the cyclic AMP cascade. The inhibition of microglial adenylyl cyclase was apparently not due to aspecific cytotoxicity. A differential regulation of adenylyl cyclase by PKC in astrocytes and microglia may help to explain qualitative and quantitative differences in the response of these cells to various physiological and pathological stimuli.