title: Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle.
abstract: Airway smooth muscle (ASM) contraction is an important component of the pathophysiology of asthma. Taurine, an agonist of glycine receptor chloride (GlyR Cl(-)) channels, was found to relax contracted ASM, which led us to question whether functional GlyR Cl(-) channels are expressed in ASM. Messenger RNA for β (GLRB), α1 (GLRA1), α2 (GLRA2), and α4 (GLRA4) subunits were found in human (Homo sapiens) and guinea pig (Cavia porcellus) tracheal smooth muscle. Immunoblotting confirmed the protein expression of GLRA1 and GLRB subunits in ASM. Electrical activity of cultured human ASM cells was assessed using a fluorescent potentiometric dye and electrophysiological recordings. Glycine increased current and significantly increased fluorescence in a dose-dependent manner. The GlyR Cl(-) channel antagonist strychnine significantly blocked the effects of glycine on potentiometric fluorescence in ASM cells. Guinea pig airway ring relaxation of ACh-induced contractions by isoproterenol was significantly left-shifted in the presence of glycine. This effect of glycine was blocked by pretreatment with the GlyR Cl(-) channel antagonist strychnine. Glycine treatment during tachykinin- and acetylcholine-induced contractions significantly decreased the maintenance of muscle force compared to control. GlyR Cl(-) channels are expressed on ASM and regulate smooth muscle force and offer a novel target for therapeutic relaxation of ASM.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA. pdy1@columbia.edu.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Yim
authors.forename: George
authors.initials: G
authors.lastname: Gallos
authors.forename: Dingbang
authors.initials: D
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002586:Cesium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004594:Electrophysiology; D005998:Glycine; D006168:Guinea Pigs; D006801:Humans; D015151:Immunoblotting; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology; D018009:Receptors, Glycine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012137:Respiratory System / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013331:Strychnine / Q000494:pharmacology
chemical_list: D002712:Chlorides; D018009:Receptors, Glycine; D002586:Cesium; D015288:Neurokinin A; C028019:cesium chloride; D013331:Strychnine; D007545:Isoproterenol; D000109:Acetylcholine; D005998:Glycine