Protein kinase C activator inhibits voltage-sensitive Ca2+ channels and catecholamine secretion in adrenal chromaffin cells.
We have investigated the effects of the phorbol ester 12-myristate 13-acetate (PMA) on depolarization-evoked Ca2+ influx and catecholamine secretion in bovine adrenal chromaffin cells. PMA (100 nM) strongly inhibited K(+)-evoked [Ca2+]i transients and Mn2+ quenching of fura-2 fluorescence. In contrast, 4 alpha-phorbol 12,13-didecanoate, a phorbol ester inactive on protein kinase C (PKC), had no effect. Maximal PMA-mediated inhibition occurred at 5-10 min incubations and were variable from cell to cell, ranging from 25 to 65% of controls. The [Ca2+]i transients evoked by the L-type Ca2+ channel activator Bay K 8644 were strongly inhibited by 100 nM PMA. PMA (0.1-10 microM) inhibited K(+)-evoked adrenaline and noradrenaline release by 23-44%. The data indicate that phorbol ester-mediated activation of PKC inhibits voltage-sensitive Ca2+ channels in chromaffin cells, leading to a prominent depression of depolarization-evoked catecholamine secretion.
Sena
C M
CM
Center for Neurosciences of Coimbra, University of Coimbra, Portugal.
Tomé
A R
AR
Santos
R M
RM
Rosário
L M
LM
D000302:Adrenal Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D004594:Electrophysiology; D066298:In Vitro Techniques; D008345:Manganese / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002395:Catecholamines; D008345:Manganese; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium