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Forskolin and Phorbol Myristate Acetate Inhibit Intracellular Ca 2+ Mobilization Induced by Amitriptyline and Bradykinin in Rat Frontocortical Neurons
Author(s) -
Shimizu Masami,
Nishida Akira,
Yamawaki Shigeto
Publication year - 1993
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 - 10.1111/j.1471-4159.1993.tb09812.x
Subject(s) - forskolin , protein kinase c , endocrinology , bradykinin , medicine , intracellular , phorbol , chemistry , inositol , inositol trisphosphate , calcium , calcium in biology , second messenger system , inositol phosphate , biology , biochemistry , stimulation , receptor , signal transduction
— Regulations of the increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) and inositol 1, 4, 5‐trisphosphate (IP 3 ) production by increasing intracellular cyclic AMP (cAMP) levels or activating protein kinase C (PKC) were studied in rat frontocortical cultured neurons. Amitriptyline (AMI; 1 m M ), a trìcyclic antidepressant, and bradykinin (BK; 1 μ M ) stimulated IP 3 production and caused transient [Ca 2+ ] i increases. Pretreatment with forskolin (100mkU M , 15 min) decreased the AMI‐and BK‐induced [Ca 2+ ] i increases by 33 and 48%, respectively. However, this treatment had no effect on the AMI‐and BK‐induced IP 3 productions. Dibutyryl‐cAMP (2 m M , 15 min) also decreased the AMI‐and BK‐induced [Ca 2+ ] i increases by 23 and 47%, respectively. H‐8 (30 μ M ), an inhibitor of protein kinase A (PKA), attenuated the ability of forskolin to inhibit the AMI‐and BK‐induced [Ca 2+ ] i increases, suggesting that the activation of cAMP/PKA was involved in these inhibitory effects of forskolin. On the other hand, forskolin treatment had no effect on 20 m M caffeine‐, 10 μ M glutamate‐, or 50 m M K + ‐induced [Ca 2+ ] i increases. Pretreatment with phorbol 12‐myristate 13‐acetate (PMA; 100 n M , 90 min) decreased both the AMI‐induced [Ca 2+ ] i increases and the IP 3 production by 31 and 25%, respectively. H‐7 (200 μ M ), an inhibitor of PKC, inhibited the ability of PMA to attenuate the [Ca 2+ ] i increases. PMA also inhibited the BK‐induced IP 3 production and the [Ca 2+ ] i increases. Taken together, these results suggest that activation of cAMP/ PKA may inhibit the IP 3 ‐mediated Ca 2+ release from internal stores; on the other hand, activation of PKC may inhibit the phosphatidylinositol 4,5‐bisphosphate breakdown and consequently reduce the [Ca 2+ ] i increases or inhibit independently both responses. PKA and PKC may differently regulate the phosphatidylinositol‐Ca 2+ signaling in rat frontocortical cultured neurons.