title: Rho-dependent kinase is involved in agonist-activated calcium entry in rat arteries.
abstract: 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 Ca2+ signal activated by noradrenaline in arteries. In rat aorta and mesenteric artery, the Rho-kinase inhibitor Y-27632 (10 microM) completely relaxed the contraction evoked by noradrenaline (1 microM) and simultaneously inhibited the Ca2+ 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 AlF4-, while in KCl-contracted arteries, Y-27632 decreased tension without changing cytosolic Ca2+. 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 Ca2+ channel blocker nimodipine. Y-27632 did not affect either the increase in the production of inositol phosphates activated by noradrenaline, or the release of Ca2+ from non-mitochondrial stores evoked by InsP3 in permeabilised aortic cells, or the Ca2+ signals evoked by thapsigargin or caffeine. The capacitative Ca2+ entry activated by thapsigargin was not impaired by Y-27632, but the entry of Ba2+ activated by noradrenaline in the presence of nimodipine was blocked by 10 microM Y-27632. These results indicate that Rho-kinase is involved in noradrenaline activation of a Ca2+ entry distinct from voltage- or store-operated channels in rat arteries.
authors.affiliation: Laboratoire de Pharmacologie, Université catholique de Louvain, UCL 5410, B-1200 Brussels, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ghisdal
authors.forename: Greet
authors.initials: G
authors.lastname: Vandenberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Morel
mesh_terms: D017607:Aluminum Compounds / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000201:enzymology; D001464:Barium / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009553:Nimodipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases
chemical_list: D017607:Aluminum Compounds; D000577:Amides; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D047908:Intracellular Signaling Peptides and Proteins; D026902:Potassium Channel Blockers; D011725:Pyridines; D014662:Vasoconstrictor Agents; C108830:Y 27632; C050992:tetrafluoroaluminate; D001464:Barium; D009553:Nimodipine; D011189:Potassium Chloride; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019204:GTP-Binding Proteins; D005459:Fluorides; D002118:Calcium; D009638:Norepinephrine