Polarized effects of amiloride and 4,4'-diisothiocyano-stilbene-2,2'- disulfonic acid on ATP-induced contraction of trachea.
Fedan-JS; Yuan-X; Belt-JJ; Frazer-DG
Eur J Pharmacol 1994 Apr; 256(1):51-56
The influence of polarization on the effects of amiloride (2609463) and 4,4'-diisothiocyano-stilbene-2,2'-disulfonic-acid (67483130) (DIDS) on the contractile responses of epithelial and airway smooth muscle to ATP were examined. Tracheal segments isolated from male English-short-hair-guinea-pigs were mounted in a culture bath where they could be perfused from the serosal (extraluminal) or mucosal (intraluminal) side. The epithelium was removed from the tracheal preparations for some experiments. ATP at 10(-4) molar (M) was initially added to the extraluminal or intraluminal bath to produce a control contraction. Preparations were then washed for 1.5 hours, after which they were incubated with 10(-4)M amiloride, a sodium (Na+) channel blocker, or DIDS, a chloride (Cl-) channel blocker, added extraluminally or intraluminally for 1 to 30 minutes (min). A second challenge with 10(-4)M ATP was performed with the ATP being added to the same bath to which it had been added to induce the first contraction. In intact tracheas, amiloride added either extraluminally or intraluminally rapidly and extensively inhibited contractions induced by extraluminally applied ATP. Amiloride had little effect on ATP induced contractile activity when ATP was added intraluminally. Extraluminally applied DIDS potentiated the contractile responses to extraluminally applied ATP after 30min. Intraluminally applied DIDS inhibited the responses to ATP added either extraluminally or intraluminally. Removal of the epithelium diminished the responses of the tracheas to the second ATP challenge. Intraluminally applied amiloride further inhibited the responses to intraluminally applied ATP. The responses were potentiated by intraluminally applied DIDS. The authors conclude that the effects of amiloride and DIDS on ATP induced contractile activity are polarized across the tracheal wall and involve epithelial and smooth muscle sodium ion and chloride ion channels.
NIOSH-Author; Nucleotides; Muscle-contraction; In-vitro-studies; Muscle-tissue; Laboratory-techniques; Tissue-culture; In-vitro-studies
European Journal of Pharmacology