title: Role of Telokin in Regulating Murine Gastric Fundus Smooth Muscle Tension.
abstract: Telokin phosphorylation by cyclic GMP-dependent protein kinase facilitates smooth muscle relaxation. In this study we examined the relaxation of gastric fundus smooth muscles from basal tone, or pre-contracted with KCl or carbachol (CCh), and the phosphorylation of telokin S13, myosin light chain (MLC) S19, MYPT1 T853, T696, and CPI-17 T38 in response to 8-Bromo-cGMP, the NO donor sodium nitroprusside (SNP), or nitrergic neurotransmission. We compared MLC phosphorylation and the contraction and relaxation responses of gastric fundus smooth muscles from telokin-/- mice and their wild-type littermates to KCl or CCh, and 8-Bromo-cGMP, SNP, or nitrergic neurotransmission, respectively. We compared the relaxation responses and telokin phosphorylation of gastric fundus smooth muscles from wild-type mice and W/WV mice which lack ICC-IM, to 8-Bromo-cGMP, SNP, or nitrergic neurotransmission. We found that telokin S13 is basally phosphorylated and that 8-Bromo-cGMP and SNP increased basal telokin phosphorylation. In muscles pre-contracted with KCl or CCh, 8-Bromo-cGMP and SNP had no effect on CPI-17 or MYPT1 phosphorylation, but increased telokin phosphorylation and reduced MLC phosphorylation. In telokin-/- gastric fundus smooth muscles, basal tone and constitutive MLC S19 phosphorylation were increased. Pre-contracted telokin-/- gastric fundus smooth muscles have increased contractile responses to KCl, CCh, or cholinergic neurotransmission and reduced relaxation to 8-Bromo-cGMP, SNP, and nitrergic neurotransmission. However, basal telokin phosphorylation was not increased when muscles were stimulated with lower concentrations of SNP or when the muscles were stimulated by nitrergic neurotransmission. SNP, but not nitrergic neurotransmission, increased telokin Ser13 phosphorylation in both wild-type and W/WV gastric fundus smooth muscles. Our findings indicate that telokin may play a role in attenuating constitutive MLC phosphorylation and provide an additional mechanism to augment gastric fundus mechanical responses to inhibitory neurotransmission.
authors.affiliation: Department of Physiology & Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Changlong
authors.initials: C
authors.lastname: An
authors.affiliation: Department of Physiology & Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Bhupal P
authors.initials: BP
authors.lastname: Bhetwal
authors.affiliation: Department of Physiology & Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, P.O. Box 800736, Charlottesville, Virginia, United States of America.
authors.forename: Avril V
authors.initials: AV
authors.lastname: Somlyo
authors.affiliation: Department of Physiology & Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Perrino
mesh_terms: D000818:Animals; D002217:Carbachol / Q000737:chemistry; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000737:chemistry; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D018994:Myosin Light Chains / Q000737:chemistry; D009219:Myosin-Light-Chain Kinase / Q000737:chemistry*; D009474:Neurons / Q000502:physiology; D009569:Nitric Oxide / Q000737:chemistry; D020030:Nitric Oxide Donors / Q000737:chemistry; D009599:Nitroprusside / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000737:chemistry
chemical_list: D018994:Myosin Light Chains; D020030:Nitric Oxide Donors; D010446:Peptide Fragments; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C060640:telokin; D011189:Potassium Chloride; D002217:Carbachol; D017869:Cyclic GMP-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase; D006152:Cyclic GMP