Premium
Synaptosomal Protein Kinase C Subspecies: B. Down‐Regulation Promoted by Phorbol Ester and Its Effect on Evoked Norepinephrine Release
Author(s) -
Oda Tomiichiro,
Shearman Mark S.,
Nishizuka Yasutomi
Publication year - 1991
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.1471-4159.1991.tb11420.x
Subject(s) - protein kinase c , subspecies , synaptosome , cytosol , chemistry , endocrinology , phorbol ester , medicine , phorbol , tetradecanoylphorbol acetate , biochemistry , biology , kinase , central nervous system , enzyme , paleontology
The effect of phorbol esters was investigated on the down‐regulation of protein kinase C (PKC) and on the release of [ 3 H]norepinephrine (NE) in synaptosomes from the rat cerebrum. Treatment with 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA) promoted the translocation of PKC activity in a P 2 fraction from the cytosol to the membrane fraction and then its down‐regulation, in a dose‐dependent manner. TPA induced a rapid down‐regulation of the type II(β) and type III(α) subspecies, but did not change the activity of the type I(γ) subspecies in the cytosolic fraction for at least 15 min. The γ‐subspecies was subsequently decreased at a slower rate. In the synaptosomes thus having only the γ‐subspecies, a subsequent dose of TPA could not enhance K + ‐evoked NE release, although, in the original synaptosomes, TPA was able to enhance K + ‐evoked NE release. Pretreatment with TPA did not alter the K + ‐evoked NE release itself. TPA was also found to enhance the K + ‐evoked NE release from synaptosomes prepared from both hippocampus, which express the γ‐subspecies of PKC at a negligible level, and cerebral cortex, which have a significant level of the γ‐subspecies, to the same degree. These results suggest that the γ‐subspecies of PKC does not participate in the TPA‐enhanced K + ‐evoked NE release from synaptosomes.