title: Effects of ML-7 and Y-27632 on carbachol- and endothelin-1-induced contraction of bovine trabecular meshwork.
abstract: The trabecular meshwork is considered a smooth muscle like tissue contributing to aqueous outflow regulation and thus to regulation of intraocular pressure. An elevation in intraocular pressure is one of the greatest risk factors for most forms of glaucoma. We assume that contraction of trabecular meshwork reduces aqueous humor outflow and thus enhances intraocular pressure, whereas relaxation exerts the opposite effect. The present paper supports the hypothesis of the trabecular meshwork being a smooth muscle-like tissue. We perform measurements of isometric force in isolated bovine trabecular meshwork strips. Contractility of this tissue is induced by carbachol or endothelin-1. The contractile force is successfully inhibited by ML-7, a highly specific inhibitor of myosin light chain kinase. The contraction is also reduced in the presence of the RhoA kinase inhibitor Y-27632. We further describe the protein expression of smooth muscle myosin and its regulatory kinase, the myosin light chain kinase, in human and bovine trabecular meshwork cells. Additionally, the serine phosphorylation of myosin light chain kinase is shown. These data indicate that the trabecular meshwork expresses major contractility regulating proteins which are involved in tissue function. Inhibition of the signaling pathways which lead to myosin phosphorylation causes inhibition of contractile force in trabecular meshwork. According to our concept of aqueous humor outflow regulation, trabecular meshwork relaxing substances appear to be ideal antiglaucomatous drugs, leading to increased outflow facility.
authors.affiliation: Augenklinik und Augenpoliklinik, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. rita.rosenthal@charite.de
authors.forename: Rita
authors.initials: R
authors.lastname: Rosenthal
authors.forename: Lars
authors.initials: L
authors.lastname: Choritz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schlott
authors.forename: Nikolaos E
authors.initials: NE
authors.lastname: Bechrakis
authors.forename: Jan
authors.initials: J
authors.lastname: Jaroszewski
authors.forename: Michael
authors.initials: M
authors.lastname: Wiederholt
authors.forename: Hagen
authors.initials: H
authors.lastname: Thieme
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007537:Isometric Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000737:chemistry; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009218:Myosins / Q000032:analysis; D009281:Naphthalenes / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology*; D012694:Serine / Q000378:metabolism; D046509:Tissue Culture Techniques; D014129:Trabecular Meshwork / Q000187:drug effects*; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D001381:Azepines; D018679:Cholinergic Agonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009281:Naphthalenes; D011725:Pyridines; C070571:ML 7; C108830:Y 27632; D012694:Serine; D002217:Carbachol; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D009218:Myosins