Chloride channel function is linked to epithelium- dependent airway relaxation

被引:13
作者
Fortner, CN [1 ]
Lorenz, JN [1 ]
Paul, RJ [1 ]
机构
[1] Univ Cincinnati, Coll Med, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA
关键词
smooth muscle; substance P; adenosine triphosphate; trachea; mouse;
D O I
10.1152/ajplung.2001.280.2.L334
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We previously reported that substance P (SP) and ATP evoke transient, epithelium-dependent relaxation of mouse tracheal smooth muscle. Since both SP and ATP are known to evoke transepithelial Cl- secretion across epithelial monolayers, we tested the hypothesis that epithelium-dependent relaxation of mouse trachea depends on Cl- channel function. In perfused mouse tracheas, the responses to SP and ATP were both inhibited by the Cl- channel inhibitors diphenylamine-2-carboxylate and 5-nitro-2-(3-phenylpropylamino)benzoate. Relaxation to ATP or SP was unaffected by 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS), and relaxation to SP was unaffected by either DIDS or DNDS. Replacing Cl- in the buffer solutions with the impermeable anion gluconate on both sides of the trachea inhibited relaxation to SP or ATP. In contrast, increasing the gradient for Cl- secretion using Cl--free medium only in the tracheal lumen enhanced the relaxation to SP or ATP. We conclude that Cl- channel function is linked to receptor-mediated, epithelium-dependent relaxation. The finding that relaxation to SP was not blocked by DIDS suggested the involvement of a DIDS-insensitive Cl- channel, potentially the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. To test this hypothesis, we evaluated tracheas from CFTR-deficient mice and found that the peak relaxation to SP or ATP was not significantly different from those responses in wild-type littermates. This suggests that a DIDS-insensitive Cl- channel other than CFTR is active in the SP response. This work introduces a possible role for Cl- pathways in the modulation of airway smooth muscle function and may have implications for fundamental studies of airway function as well as therapeutic approaches to pulmonary disease.
引用
收藏
页码:L334 / L341
页数:8
相关论文
共 30 条
  • [1] CHLORIDE CHANNELS IN THE APICAL MEMBRANE OF NORMAL AND CYSTIC-FIBROSIS AIRWAY AND INTESTINAL EPITHELIA
    ANDERSON, MP
    SHEPPARD, DN
    BERGER, HA
    WELSH, MJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (01): : L1 - L14
  • [2] Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted from fetal rat lung
    Barker, PM
    Gatzy, JT
    [J]. PEDIATRIC RESEARCH, 1998, 43 (05) : 652 - 659
  • [3] STILBENE DISULFONATE BLOCKADE OF COLONIC SECRETORY CL- CHANNELS IN PLANAR LIPID BILAYERS
    BRIDGES, RJ
    WORRELL, RT
    FRIZZELL, RA
    BENOS, DJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (04): : C902 - C912
  • [4] BULTMANN R, 1994, BRIT J PHARMACOL, V112, P690
  • [5] Pseudomonas aeruginosa induces changes in fluid transport across airway surface epithelia
    Evans, DJ
    Matsumoto, PS
    Widdicombe, JH
    Li-Yun, C
    Maminishkis, AA
    Miller, SS
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1998, 275 (05): : C1284 - C1290
  • [6] Fedan JS, 1999, J PHARMACOL EXP THER, V289, P901
  • [7] EPITHELIAL MODULATION OF TRACHEAL SMOOTH-MUSCLE RESPONSES TO ANTIGENIC-STIMULATION
    FROSSARD, N
    MULLER, F
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1986, 61 (04) : 1449 - 1456
  • [8] ANOMALIES IN ION-TRANSPORT IN CF MOUSE TRACHEAL EPITHELIUM
    GRUBB, BR
    PARADISO, AM
    BOUCHER, RC
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (01): : C293 - C300
  • [9] Intestinal physiology and pathology in gene-targeted mouse models of cystic fibrosis
    Grubb, BR
    Gabriel, SE
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1997, 273 (02): : G258 - G266
  • [10] Ablation of the SERCA3 gene alters epithelium-dependent relaxation in mouse tracheal smooth muscle
    Kao, J
    Fortner, CN
    Liu, LH
    Shull, GE
    Paul, RJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1999, 277 (02) : L264 - L270