title: Effects of HA1077, a protein kinase inhibitor, on myosin phosphorylation and tension in smooth muscle.
abstract: We examined the effects of HA1077, a potent inhibitor of protein kinases in vitro, on the relationship between tension and myosin-light chain (MLC20) phosphorylation in the initial phase of contraction of the rabbit aorta. The dose-response curve of HA1077 for MLC20 phosphorylation was to the left of the tension curve produced by 40 mM K+. In contrast, the potassium dose-response (15-100 mM) curves for tension and MLC20 phosphorylation were virtually identical. The nifedipine dose-response (1-3000 nM) curves for tension and MLC20 phosphorylation after 40 mM K(+)-stimulation were much the same. HA1077 inhibited the contraction induced by 30 microM prostaglandin F2 alpha (ED50 = 50 microM). Stimulation with prostaglandin F2 alpha induced both mono (MLC-P) and diphosphorylation (MLC-P2) of MLC20. In the presence of various concentrations of HA1077 (1-300 microM), the dose-response curves for MLC-P and MLC-P2 were also to the left of the tension curve. HA1077 inhibited MLC-P2 (ED50 less than microM) more effectively than it inhibited MLC-P (ED50 = 2.1 microM). These observations indicate that the relationship between tension and MLC20 phosphorylation involves inhibition of protein kinases by HA1077. The mechanism underlying the formation of MLC-P2 induced by prostaglandin F2 alpha may differ from that underlying MLC-P formation.
authors.affiliation: Biochemical Research Laboratory, Asahi Chemical Industry Co., Ltd., Miyazaki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Seto
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000276:immunology / Q000378:metabolism; D009218:Myosins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011817:Rabbits
chemical_list: D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015237:Dinoprost; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; C049347:fasudil; D011188:Potassium