Effect of neutral endopeptidase inhibition on substance-P-induced increase in short-circuit current of canine cultured tracheal epithelium.
We studied the effect of substance P (SP) on the electric properties of cultured canine tracheal epithelium and its possible modulation by neutral endopeptidase (NEP) by Ussing's short-circuited technique in vitro. Addition of SP (5 x 10(-6) M) to the mucosal side increased short-circuit current (SCC) from 5.1 +/- 0.9 to 10.3 +/- 2.2 microA/cm2 (mean +/- SE; p less than 0.01), which was accompanied by increases in transepithelial potential difference and conductance. The effect of the mucosal SP on SCC was dose-dependent, with the maximal increase from the baseline value being 5.8 +/- 1.0 microA/cm2 observed at 5 x 10(-5) M. The NEP inhibitor phosphoramidon (10(-5) M) did not affect these responses. On the other hand, SCC was not altered by the addition of SP to the submucosal side. However, it was increased dose-dependently in the presence of phosphoramidon (10(-5) M) but not in the presence of captopril, bestatin or leupeptin. This stimulatory effect of submucosal SP was abolished by furosemide, diphenylamine-2-carboxylate and Cl-free medium, but not by amiloride. These results suggest that SP may selectively stimulate Cl secretion across the airway epithelium and that this effect may be modulated by submucosal NEP.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Sakai
N
N
Isono
K
K
Kanemura
T
T
Chiyotani
A
A
Yamauchi
F
F
Takizawa
T
T
Konno
K
K
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D003172:Complement C1 / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity / Q000187:drug effects; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D013997:Time Factors; D014132:Trachea / Q000502:physiology*
D000900:Anti-Bacterial Agents; D003172:Complement C1; D006020:Glycopeptides; D007976:Leupeptins; D013373:Substance P; D000584:Amiloride; D005665:Furosemide; D002216:Captopril; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; C032854:leupeptin; C008890:phosphoramidon