Soluble Guanylate Cyclase Agonists Induce Bronchodilation in Human Small Airways
| العنوان: | Soluble Guanylate Cyclase Agonists Induce Bronchodilation in Human Small Airways |
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| المؤلفون: | Serpil E. Erzurum, Cynthia J. Koziol-White, Dennis J. Stuehr, Peter Sandner, Arnab Ghosh, Reynold A. Panettieri |
| المصدر: | American Journal of Respiratory Cell and Molecular Biology. 62:43-48 |
| بيانات النشر: | American Thoracic Society, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Pulmonary and Respiratory Medicine, Agonist, medicine.drug_class, Clinical Biochemistry, Cell Biology, Pharmacology, respiratory tract diseases, 03 medical and health sciences, Cyclic nucleotide, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, 030228 respiratory system, chemistry, Guanosine monophosphate, Second messenger system, medicine, Bronchoconstriction, Signal transduction, medicine.symptom, Soluble guanylyl cyclase, Molecular Biology, Cyclic guanosine monophosphate |
| الوصف: | The soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate signaling pathway evokes vascular smooth muscle relaxation; whether this pathway mediates airway smooth muscle relaxation remains controversial. We posit that sGC activators are equi-effective as β-agonists in reversing contractile agonist-induced airway smooth muscle shortening. To provide clarity, we tested the efficacy of sGC stimulator and activator drugs, BAY 41-2272 and BAY 60-2270, respectively, in reversing bronchoconstriction of human small airways using human precision-cut lung slices (hPCLS). Both BAY drugs reversed carbachol-induced bronchoconstriction to a maximal degree comparable to that of formoterol. Moreover, the sGC drugs remained effective bronchodilators despite formoterol-induced desensitization of the airways. Analysis of the hPCLS after their activation by sGC or β2-adrenergic receptor agonist showed distinct cyclic nucleotide accumulation in the hPCLS. Collectively, these data suggest that cAMP and cyclic guanosine monophosphate pathways are equi-effective for reversing carbachol-induced bronchoconstriction in the human airway via separate and distinct second messenger pathways. This should open the door for future studies to test whether sGC-targeted drugs alone or in combination can serve as effective bronchodilators in asthma and chronic obstructive pulmonary disease. |
| تدمد: | 1535-4989 1044-1549 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::12dc9e2e25d5f2c3c8494226e04754ccTest https://doi.org/10.1165/rcmb.2019-0001ocTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........12dc9e2e25d5f2c3c8494226e04754cc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354989 10441549 |
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