Tags

Type your tag names separated by a space and hit enter

Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles.
Pulm Pharmacol Ther. 2016 12; 41:1-10.PP

Abstract

Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition. In contrast, cystathionine β-synthase expression, another H2S synthesis enzyme, however was not consistently detected in the bronchiolar smooth muscle layer. Electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked smooth muscle relaxation. Inhibition of CSE, nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and of ATP-dependent K+, transient receptor potential A1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels reduced the EFS relaxation but failed to modify the GYY4137 response. Raising extracellular K+ concentration inhibited the GYY4137 relaxation. Large conductance Ca2+-activated K+ channel blockade reduced both EFS and GYY4137 responses. GYY4137 inhibited the contractions induced by histamine and reduced to a lesser extent the histamine-induced increases in intracellular [Ca2+]. These results suggest that relaxation induced by EFS in the pig terminal bronchioles partly involves the H2S/CSE pathway. H2S response is produced via NO/sGC-independent mechanisms involving K+ channels and intracellular Ca2+ desensitization-dependent pathways. Thus, based on our current results H2S donors might be useful as bronchodilator agents for the treatment of lung diseases with persistent airflow limitation, such as asthma and chronic obstructive lung disease.

Authors+Show Affiliations

Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Servicio de Cirugía Torácica, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.Servicio de Cirugía Torácica, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: medardo@ucm.es.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27603231

Citation

Fernandes, Vítor S., et al. "Role of Endogenous Hydrogen Sulfide in Nerve-evoked Relaxation of Pig Terminal Bronchioles." Pulmonary Pharmacology & Therapeutics, vol. 41, 2016, pp. 1-10.
Fernandes VS, Recio P, López-Oliva E, et al. Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles. Pulm Pharmacol Ther. 2016;41:1-10.
Fernandes, V. S., Recio, P., López-Oliva, E., Martínez, M. P., Ribeiro, A. S., Barahona, M. V., Martínez, A. C., Benedito, S., Agis-Torres, Á., Cabañero, A., Muñoz, G. M., García-Sacristán, A., Orensanz, L. M., & Hernández, M. (2016). Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles. Pulmonary Pharmacology & Therapeutics, 41, 1-10. https://doi.org/10.1016/j.pupt.2016.09.003
Fernandes VS, et al. Role of Endogenous Hydrogen Sulfide in Nerve-evoked Relaxation of Pig Terminal Bronchioles. Pulm Pharmacol Ther. 2016;41:1-10. PubMed PMID: 27603231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles. AU - Fernandes,Vítor S, AU - Recio,Paz, AU - López-Oliva,Elvira, AU - Martínez,María Pilar, AU - Ribeiro,Ana Sofía, AU - Barahona,María Victoria, AU - Martínez,Ana Cristina, AU - Benedito,Sara, AU - Agis-Torres,Ángel, AU - Cabañero,Alberto, AU - Muñoz,Gemma M, AU - García-Sacristán,Albino, AU - Orensanz,Luis M, AU - Hernández,Medardo, Y1 - 2016/09/04/ PY - 2016/04/19/received PY - 2016/08/05/revised PY - 2016/09/02/accepted PY - 2016/9/8/pubmed PY - 2017/11/9/medline PY - 2016/9/8/entrez KW - Cystathionine β-synthase KW - Cystathionine γ-lyase KW - GYY4137 KW - Hydrogen sulfide KW - Nerve-evoked relaxation KW - Pig terminal bronchioles SP - 1 EP - 10 JF - Pulmonary pharmacology & therapeutics JO - Pulm Pharmacol Ther VL - 41 N2 - Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition. In contrast, cystathionine β-synthase expression, another H2S synthesis enzyme, however was not consistently detected in the bronchiolar smooth muscle layer. Electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked smooth muscle relaxation. Inhibition of CSE, nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and of ATP-dependent K+, transient receptor potential A1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels reduced the EFS relaxation but failed to modify the GYY4137 response. Raising extracellular K+ concentration inhibited the GYY4137 relaxation. Large conductance Ca2+-activated K+ channel blockade reduced both EFS and GYY4137 responses. GYY4137 inhibited the contractions induced by histamine and reduced to a lesser extent the histamine-induced increases in intracellular [Ca2+]. These results suggest that relaxation induced by EFS in the pig terminal bronchioles partly involves the H2S/CSE pathway. H2S response is produced via NO/sGC-independent mechanisms involving K+ channels and intracellular Ca2+ desensitization-dependent pathways. Thus, based on our current results H2S donors might be useful as bronchodilator agents for the treatment of lung diseases with persistent airflow limitation, such as asthma and chronic obstructive lung disease. SN - 1522-9629 UR - https://www.unboundmedicine.com/medline/citation/27603231/Role_of_endogenous_hydrogen_sulfide_in_nerve_evoked_relaxation_of_pig_terminal_bronchioles_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1094-5539(16)30095-5 DB - PRIME DP - Unbound Medicine ER -