CL- SECRETION BY TRACHEA OF CFTR(+/-) AND CFTR(-/-) FETAL MOUSE

被引:21
作者
BARKER, PM
BRIGMAN, KK
PARADISO, AM
BOUCHER, RC
GATZY, JT
机构
[1] UNIV N CAROLINA, DEPT MED, CHAPEL HILL, NC 27599 USA
[2] UNIV N CAROLINA, DEPT PHARMACOL, CHAPEL HILL, NC 27599 USA
关键词
D O I
10.1165/ajrcmb.13.3.7544595
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The absence of pathologic changes in newborn cystic fibrosis (CF) lung suggests that the fetal CF lung is inflated with a normal volume of liquid and that Cl- is secreted through paths other than the cystic fibrosis transmembrane conductance regulator (CFTR)-associated Cl- channel. We studied liquid content of distal lung and transepithelial electrical potential difference (PD) of cultured cystic tracheal explants from 16 to 19 day gestation fetal mice of CFTR (+/-) (heterozygous) females that were mated with CFTR (-/-) ''knockout'' males. Distal lung water content was not affected by fetal genotype. Basal PDs were not different (CFTR (+/-), 8.6 mV, and CFTR (-/-), 9.1 mV), and PDs of both groups were inhibited by intraluminal injection of amiloride (10(-4) M) (-25%) and after addition of bumetanide (10(-4) M) to the bath (-40%). Terbutaline (3 x 10(-5) M) induced a similar increase in PD (about 65%) in both groups. Intraluminal injection of ionomycin (2 x 10(-5) and 5 x 10(-6) M) raised PD in both groups (CFTR (+/-) by 32 and 27% and CFTR (-/-) by 41 and 11%). All of the increase in PD induced by terbutaline and ionomycin was inhibited by bumetanide. The PD response to terbutaline was not attenuated by pretreatment with ionomycin or the Ca2+ chelator BAPTA (10(-4) M). Ionomycin or ATP, but not terbutaline, increased intracellular Ca2+ concentration of isolated cultured tracheal epithelial cells. The response of CF epithelium to beta-adrenergic agonist suggests that cyclic AMP-activated Cl- pathways other than those linked to CFTR regulate liquid secretion in fetal mouse airways.
引用
收藏
页码:307 / 313
页数:7
相关论文
共 28 条
  • [11] RESTORATION OF LUNG LIQUID VOLUME FOLLOWING ITS ACUTE ALTERATION IN FETAL SHEEP
    DICKSON, KA
    HARDING, R
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1987, 385 : 531 - 543
  • [12] GATZY JT, 1992, P ROYAL COLLEGE PHYS, V22, P309
  • [13] 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
  • [14] UPPER AIRWAY RESISTANCES IN FETAL SHEEP - THE INFLUENCE OF BREATHING ACTIVITY
    HARDING, R
    BOCKING, AD
    SIGGER, JN
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1986, 60 (01) : 160 - 165
  • [15] ACTIVATION BY EXTRACELLULAR NUCLEOTIDES OF CHLORIDE SECRETION IN THE AIRWAY EPITHELIA OF PATIENTS WITH CYSTIC-FIBROSIS
    KNOWLES, MR
    CLARKE, LL
    BOUCHER, RC
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (08) : 533 - 538
  • [16] VOLUME AND ION-TRANSPORT BY FETAL-RAT ALVEOLAR AND TRACHEAL EPITHELIA IN SUBMERSION CULTURE
    KROCHMAL, EM
    BALLARD, ST
    YANKASKAS, JR
    BOUCHER, RC
    GATZY, JT
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (03): : F397 - F407
  • [17] DEVELOPMENTAL DIFFERENCES OF CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR FUNCTIONAL EXPRESSION IN ISOLATED RAT FETAL DISTAL AIRWAY EPITHELIAL-CELLS
    MACLEOD, RJ
    HAMILTON, JR
    KOPELMAN, H
    SWEEZEY, NB
    [J]. PEDIATRIC RESEARCH, 1994, 35 (01) : 45 - 49
  • [18] TRANS-EPITHELIAL TRANSPORT BY PULMONARY ALVEOLAR TYPE-II CELLS IN PRIMARY CULTURE
    MASON, RJ
    WILLIAMS, MC
    WIDDICOMBE, JH
    SANDERS, MJ
    MISFELDT, DS
    BERRY, LC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (19): : 6033 - 6037
  • [19] REGULATION OF TRANSEPITHELIAL ION-TRANSPORT AND INTRACELLULAR CALCIUM BY EXTRACELLULAR ATP IN HUMAN NORMAL AND CYSTIC-FIBROSIS AIRWAY EPITHELIUM
    MASON, SJ
    PARADISO, AM
    BOUCHER, RC
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1991, 103 (03) : 1649 - 1656
  • [20] EXPRESSION OF CFTR AND A CAMP-STIMULATED CHLORIDE SECRETORY CURRENT IN CULTURED HUMAN FETAL ALVEOLAR EPITHELIAL-CELLS
    MCCRAY, PB
    BETTENCOURT, JD
    BASTACKY, J
    DENNING, GM
    WELSH, MJ
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1993, 9 (06) : 578 - 585