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Abstract:

Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post-transcriptional and/or post-translational regulation. Our purpose was to study the possible mechanisms leading to NOS downregulation in submandibular glands of normal mice and in the nonobese diabetic (NOD) mouse model of salivary dysfunction with lower NOS activity. NOS activity and cGMP accumulation were determined by radioassays in submandibular glands of both mice in the presence of the protein kinase inhibitors KN-93 and bisindolylmaleimide. NOS I mRNA and protein expression and localization were assessed by RT-PCR, Western blot and immunohistochemistry. A downregulatory effect of calcium-calmodulin kinase II (CaMK II) on NOS activity in submandibular glands of both NOD and BALB/c mice was observed. Our results are consistent with a physiological regulation of NOS activity by this kinase but not by PKC in normal BALB/c mice. They are also supportive of a role for CaMK II in the lack of detectable NOS activity in submandibular glands of NOD mice. KN-93 also restored cGMP accumulation in NOD submandibular glands. 4 The downregulation of NOS in NOD mice seems to be mainly mediated by this kinase rather than the result of a lower expression or different cellular localization of the enzyme. It was not related to different substrate or cofactors availability either.

Registro:

Documento: Artículo
Título:Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
Autor:Rosignoli, F.; Roca, V.; Meiss, R.; Pregi, N.; Pérez Leirós, C.
Filiación:Departamento de Quimica Biologica, Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires - CONICET, Argentina
Academia Nacional de Medicina, Buenos Aires, Argentina
Biological Chemistry, University of Buenos Aires, Ciudad Universitaria, Pab. II, 4 piso, Buenos Aires 1428, Argentina
Palabras clave:CaM kinase inhibition; KN-93; NOD mice; NOS regulation; Salivary dysfunction; arginase; bisindolylmaleimide; complementary DNA; cyclic GMP; glyceraldehyde 3 phosphate dehydrogenase; messenger RNA; n [2 [[n [3 (4 chlorophenyl) 2 propenyl] n methylamino]methyl]phenyl] n (2 hydroxyethyl) 4 methoxybenzenesulfonamide; n(g) methylarginine; nitric oxide; nitric oxide synthase inhibitor; protein kinase (calcium,calmodulin); protein kinase inhibitor; animal model; animal tissue; article; DNA synthesis; down regulation; enzyme assay; enzyme inhibition; immunohistochemistry; mouse; nonhuman; priority journal; protein expression; reverse transcription polymerase chain reaction; salivary gland; signal transduction; submandibular gland; Western blotting; Animals; Ca(2+)-Calmodulin Dependent Protein Kinase; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Nitric Oxide; Protein Kinase Inhibitors; Salivary Gland Diseases; Signal Transduction; Submandibular Gland
Año:2004
Volumen:143
Número:8
Página de inicio:1058
Página de fin:1065
DOI: http://dx.doi.org/10.1038/sj.bjp.0705952
Título revista:British Journal of Pharmacology
Título revista abreviado:Br. J. Pharmacol.
ISSN:00071188
CODEN:BJPCB
CAS:arginase, 9000-96-8; cyclic GMP, 7665-99-8; glyceraldehyde 3 phosphate dehydrogenase, 9001-50-7; n [2 [[n [3 (4 chlorophenyl) 2 propenyl] n methylamino]methyl]phenyl] n (2 hydroxyethyl) 4 methoxybenzenesulfonamide, 139298-40-1; n(g) methylarginine, 156706-47-7, 17035-90-4, 53308-83-1; nitric oxide, 10102-43-9; Ca(2+)-Calmodulin Dependent Protein Kinase, 2.7.1.123; Nitric Oxide, 10102-43-9; Protein Kinase Inhibitors
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00071188_v143_n8_p1058_Rosignoli

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Citas:

---------- APA ----------
Rosignoli, F., Roca, V., Meiss, R., Pregi, N. & Pérez Leirós, C. (2004) . Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction. British Journal of Pharmacology, 143(8), 1058-1065.
http://dx.doi.org/10.1038/sj.bjp.0705952
---------- CHICAGO ----------
Rosignoli, F., Roca, V., Meiss, R., Pregi, N., Pérez Leirós, C. "Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction" . British Journal of Pharmacology 143, no. 8 (2004) : 1058-1065.
http://dx.doi.org/10.1038/sj.bjp.0705952
---------- MLA ----------
Rosignoli, F., Roca, V., Meiss, R., Pregi, N., Pérez Leirós, C. "Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction" . British Journal of Pharmacology, vol. 143, no. 8, 2004, pp. 1058-1065.
http://dx.doi.org/10.1038/sj.bjp.0705952
---------- VANCOUVER ----------
Rosignoli, F., Roca, V., Meiss, R., Pregi, N., Pérez Leirós, C. Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction. Br. J. Pharmacol. 2004;143(8):1058-1065.
http://dx.doi.org/10.1038/sj.bjp.0705952