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Rho‐dependent kinase is involved in agonist‐activated calcium entry in rat arteries
Author(s) -
Ghisdal Philippe,
Vandenberg Greet,
Morel Nicole
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00855.x
Subject(s) - agonist , chemistry , calcium , kinase , pharmacology , microbiology and biotechnology , endocrinology , medicine , biophysics , receptor , biology , biochemistry
The present study was aimed at investigating whether, besides its pivotal role in Ca 2+ ‐independent contraction of smooth muscle, Rho‐kinase is involved in the mechanisms underlying the Ca 2+ signal activated by noradrenaline in arteries. In rat aorta and mesenteric artery, the Rho‐kinase inhibitor Y‐27632 (10 μM) completely relaxed the contraction evoked by noradrenaline (1 μM) and simultaneously inhibited the Ca 2+ signal by 54 ± 1 % (mesenteric artery) and 71 ± 15 % (aorta), and the cell membrane depolarisation by 56 ± 11 % (mesenteric artery). A similar effect was observed in arteries contracted by AlF 4 − , while in KCl‐contracted arteries, Y‐27632 decreased tension without changing cytosolic Ca 2+ . The same effects were observed with another inhibitor of Rho‐kinase (HA1077) but not with an inhibitor of protein kinase C (Ro‐31‐8220). Effects of Y‐27632 were not prevented by incubating the artery in 25 mM KCl, with K + channel blockers or with the Ca 2+ channel blocker nimodipine. Y‐27632 did not affect either the increase in the production of inositol phosphates activated by noradrenaline, or the release of Ca 2+ from non‐mitochondrial stores evoked by Ins P 3 in permeabilised aortic cells, or the Ca 2+ signals evoked by thapsigargin or caffeine. The capacitative Ca 2+ entry activated by thapsigargin was not impaired by Y‐27632, but the entry of Ba 2+ activated by noradrenaline in the presence of nimodipine was blocked by 10 μM Y‐27632. These results indicate that Rho‐kinase is involved in noradrenaline activation of a Ca 2+ entry distinct from voltage‐ or store‐operated channels in rat arteries.