Stretch-induced triphosphorylation of myosin light chain and myogenic tone in canine basilar artery.
The relationship between phosphorylation of 20,000 Da myosin light chain (MLC20) and contraction in response to mechanical stretch was investigated in the canine basilar artery. A slow stretch (at a rate of 1 mm/s and a stimulus period for 15 min) increased triphosphorylated MLC20 despite lowered intracellular calcium concentration and mechanical activities, such as myogenic tone, shortening velocity and stiffness of the artery. Nicardipine, a Ca2+ channel blocker, and ML-9, a myosin light chain kinase (MLCK) inhibitor, partially inhibited the stretch-induced MLC20 phosphorylation. The remained phosphorylation was further reduced by calphostin C, a protein kinase C (PKC) inhibitor. Y-27632, a Rho-kinase inhibitor, inhibited phosphorylation of myosin light chain phosphatase and attenuated MLC20 phosphorylation. These results suggest that slow stretch induces triphosphorylation of MLC20, which is mediated by MLCK, PKC, and Rho-kinase, and that the triphosphorylation of MLC20 does not result in myogenic contraction, rather seems to counteract it.
Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-City, Shizuoka 422-8526, Japan. obara@ys7.u-shizuoka-ken.ac.jp
Kazuo
K
Obara
Mayumi
M
Uchino
Masayo
M
Koide
Akihiro
A
Yamanaka
Koichi
K
Nakayama
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012026:Reflex, Stretch; D013997:Time Factors; D054460:rho-Associated Kinases
D000577:Amides; D001381:Azepines; D002121:Calcium Channel Blockers; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C056218:ML 9; C108830:Y 27632; D009529:Nicardipine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; C058819:calphostin C; D002118:Calcium