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Roles for Protein Kinase C and Mitogen‐Activated Protein Kinase in Nicotine‐Induced Secretion from Bovine Adrenal Chromaffin Cells
Author(s) -
Cox Michael E.,
Parsons Sarah J.
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.1471-4159.1997.69031119.x
Subject(s) - mapk/erk pathway , kinase , protein kinase a , exocytosis , chromaffin cell , protein kinase c , microbiology and biotechnology , mitogen activated protein kinase kinase , mitogen activated protein kinase , chemistry , biology , endocrinology , medicine , secretion , catecholamine , adrenal medulla
Both the Ca 2+ /phospholipid‐dependent protein kinases (protein kinases C, PKCs) and mitogen‐activated protein kinases (MAPKs) have been implicated as participants in the secretory response of bovine adrenomedullary chromaffin cells. To investigate a possible role for these kinases in exocytosis and the relationship of these kinases to one another, intact chromaffin cells were treated with agents that inhibited each of the kinases and analyzed for catecholamine release and MAPK/extracellular signal‐regulated kinase (ERK) kinase (MEK)/MAPK activation after stimulation with secretagogues of differential efficacy. Of the three secretagogues tested, inactivation of PKCs by long‐term phorbol 12‐myristate 13‐acetate (PMA) treatment or incubation with GF109203X had the greatest inhibitory effect on nicotine‐induced catecholamine release and MEK/MAPK activation, a moderate effect on KCl‐induced events, and little, if any, effect on Ca 2+ ionophore‐elicited exocytosis and MEK/MAPK activation. These results indicate that PKC plays a significant role in events induced by the optimal secretagogue nicotine and a lesser role in exocytosis elicited by the suboptimal secretagogues KCl and Ca 2+ ionophore. Treatment of cells with the MEK‐activation inhibitor PD098059 completely inhibited MEK/MAPK activation (IC 50 1–5 µ M ) and partially inhibited catecholamine release induced by all secretagogues. However, PD098059 was more effective at inhibiting exocytosis induced by suboptimal secretagogues (IC 50 ∼10 µ M ) than that induced by nicotine (IC 50 ∼30 µ M ). These results suggest a more prominent role for MEK/MAPK in basic secretory events activated by suboptimal secretagogues than in those activated by the optimal secretagogue nicotine. However, PD098059 also partially blocked secretion potentiated by short‐term PMA treatment, suggesting that PKC can function in part by signaling through MEK/MAPK to enhance secretion. Taken together, these results provide evidence for the preferential involvement of MEK/MAPK in basic secretory events activated by the suboptimal secretagogues KCl and Ca 2+ ionophore and the participation of both PKC and MEK/MAPK in optimal secretion induced by nicotine.