Premium
Ca 2+ /Calmodulin‐Dependent Protein Kinase II Inhibitor KN‐62 Inhibits Adrenal Medullary Chromaffin Cell Functions Independent of Its Action on the Kinase
Author(s) -
Tsutsui Masato,
Yanagihara Nobuyuki,
Fukunaga Kohji,
Minami Kouichiro,
Nakashima Yasuhide,
Kuroiwa Akio,
Miyamoto Eishichi,
Izumi Futoshi
Publication year - 1996
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.1471-4159.1996.66062517.x
Subject(s) - chemistry , adrenal medulla , catecholamine , chromaffin cell , endocrinology , protein kinase a , medicine , veratridine , secretion , tyrosine hydroxylase , kinase , calmodulin , biochemistry , biology , enzyme , sodium , sodium channel , organic chemistry
KN‐62, an inhibitor of Ca 2+ /calmodulin‐dependent protein kinase II (CaM kinase II), inhibited significantly catecholamine secretion and tyrosine hydroxylase activity stimulated by acetylcholine in cultured bovine adrenal medullary cells. KN‐62, however, showed an additional inhibitory effect on acetylcholine‐induced 45 Ca 2+ influx, which is essential for functional responses. Carbachol‐stimulated 22 Na + influx, veratridine‐induced 22 Na + influx, and 56 m M K + ‐evoked 45 Ca 2+ influx were also attenuated by KN‐62. Inhibitions by KN‐62 of these ion influxes were correlated closely with those of catecholamine secretion. KN‐04, which is a structural analogue of KN‐62 but does not inhibit CaM kinase II activity, elicited inhibitory effects on the three kinds of stimulant‐evoked ion influxes with an inhibitory potency similar to KN‐62. These results suggest that KN‐62 inhibits catecholamine secretion and tyrosine hydroxylase activation due to mainly its ion channel blockade on the plasma membrane rather than the inhibition of CaM kinase II activity in the cells.