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Phorbol Esters Enhance Exocytosis from Chromaffin Cells by Two Mechanisms
Author(s) -
Bittner Mary A.,
Holz Ronald W.
Publication year - 1990
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.1471-4159.1990.tb13302.x
Subject(s) - cycloheximide , protein kinase c , secretion , digitonin , chromaffin cell , exocytosis , intracellular , protein biosynthesis , protein kinase a , depolarization , phorbol , tetradecanoylphorbol acetate , medicine , chemistry , biology , endocrinology , adrenal medulla , biochemistry , microbiology and biotechnology , phosphorylation , catecholamine , membrane
Abstract: Treatment with phorbol esters such as 12‐ O ‐tet‐radecanoylphorbol acetate (TPA) rapidly enhances [ 3 H]norepinephrine secretion from digitonin‐permeabilized adrenal chromaffin cells. When TPA treatment was prolonged for several hours, a second distinct enhancing effect was observed. This later enhancement was most prominent at intracellular Ca 2+ concentrations of 3–30 μM , and did not require the continued presence of membrane‐bound protein kinase C for its expression. The effect could be elicited by as little as 30‐min exposure to TPA, followed by several hours in TPA‐ free medium. This effect of TPA was blocked by actinomycin D and cycloheximide, indicating a requirement for RNA and protein synthesis. Similar effects were seen when intact cells that had been pretreated with TPA were stimulated to secrete by depolarizing concentrations of K + . Thus, protein kinase C enhances secretion by two mechanisms. One is rapid and probably reflects the effects of immediate protein phosphorylation. The other occurs over several hours and requires gene transcription and protein synthesis.