Effects of methacholine and uridine 5'-triphosphate on tracheal mucus rheology in mice
| Autor: | Malcolm King, Martin M. Lee, William A. Boyd, Eiichi Sudo |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Clinical Biochemistry Population Cystic Fibrosis Transmembrane Conductance Regulator Stimulation Uridine Triphosphate 4 4'-Diisothiocyanostilbene-2 2'-Disulfonic Acid Bronchoconstrictor Agents chemistry.chemical_compound Mice Internal medicine medicine Animals education Molecular Biology Methacholine Chloride Transepithelial potential difference education.field_of_study biology Chemistry Epithelial Cells Cell Biology respiratory system Chloride channel blocker Mucus Cystic fibrosis transmembrane conductance regulator Elasticity Electrophysiology Mice Inbred C57BL Trachea Endocrinology DIDS Chloride channel biology.protein Rheology Microelectrodes hormones hormone substitutes and hormone antagonists |
| Zdroj: | American journal of respiratory cell and molecular biology. 22(3) |
| ISSN: | 1044-1549 |
| Popis: | We compared the action of methacholine (MCh) and uridine 5'-triphosphate (UTP) with and without pretreatment with the chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) on the transepithelial potential difference (PD), the mucus collection rate (MCR), and tracheal mucus rheology using anesthetized C57BL/6 mice. The cystic fibrosis transmembrane conductance regulator (CFTR) blocker 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) was also used as a pretreatment for MCh. After collecting baseline mucus for 1.5 h, mucus secretion was stimulated by instilling 5 microl of 10(-2) M MCh or UTP around the upper trachea. There was a significant increase in PD after MCh or UTP stimulation (-21.3+/-2.0 mV MCh versus -14.1+/-1.6 mV control; -25.4+/-2.5 mV UTP versus -19.2+/-1.9 mV control). When UTP administration was preceded by DIDS, PD shifted from -15.2+/-2.9 to -12.0+/-2.2 mV. When MCh was preceded by DIDS or by NPPB, there was no change in PD. There was a significant decrease in mucus rigidity index, logG*, with MCh (2.54+/-0.09 versus 2.99+/-0.14 for control), similar to that previously reported in other species. With UTP, 14 of 16 mice responded in terms of PD becoming more negative, and of these, there was a significant difference in logG* after UTP administration (2.29 +/-0.10 versus 2.57+/-0.10 for control), whereas there was no change in logG* with DIDS administration before UTP. When DIDS administration preceded MCh, there was a diminished but still significant decrease in logG* from control, whereas there was no change in logG* when NPPB was preadministered. The control mucus collection rate was 0.19+/-0.09 mg/h, whereas after MCh stimulation, it increased to 2.83+/-0.78 mg/h. No significant difference was measured in the MCR after either UTP or DIDS+UTP stimulation. DIDS+MCh and NPPB+MCh both resulted in significant increases in MCR, but of a much smaller magnitude than that for MCh alone. We conclude that hypersecretion owing to UTP in C57BL/6 mice is less vigorous than with MCh, reflecting the limited population of Ca(2+)-dependent Cl(-) channels stimulated by UTP P(2) receptors. The action of MCh on tracheal mucus secretion in mice appears to involve both CFTR- and non-CFTR-dependent chloride channels. |
| Databáze: | OpenAIRE |
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