113 203

Cited 20 times in

Properties of substance P-stimulated mucus secretion from porcine tracheal submucosal glands.

Authors
 Monal Khansaheb  ;  Jae Young Choi  ;  Nam Soo Joo  ;  Yu-Mi Yang  ;  Mauri Krouse  ;  Jeffrey J. Wine 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol.300(3) : 370-9, 2011 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 
ISSN
 1040-0605 
Issue Date
2011
MeSH
Animals ; Anions ; Calcium/metabolism ; Capsaicin/pharmacology ; Carbachol/pharmacology ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Fura-2/metabolism ; Humans ; In Vitro Techniques ; Microscopy, Interference ; Mucus/secretion* ; Respiratory Mucosa/cytology ; Respiratory Mucosa/drug effects* ; Respiratory Mucosa/secretion* ; Substance P/pharmacology* ; Sus scrofa ; Time Factors ; Trachea/cytology ; Trachea/drug effects* ; Trachea/secretion* ; Type C Phospholipases/metabolism
Abstract
Human and pig airway submucosal glands secrete mucus in response to substance P (SubP), but in pig tracheal glands the response to SubP is >10-fold greater than in humans and shares features with cholinergically produced secretion. CFTR-deficient pigs provide a model for human cystic fibrosis (CF), and in newborn CF pigs the response of tracheal glands to SubP is significantly reduced (Joo et al. J Clin Invest 120: 3161-3166, 2010). To further define features of SubP-mediated gland secretion, we optically measured secretion rates from individual adult porcine glands in isolated tracheal tissues in response to mucosal capsaicin and serosal SubP. Mucosal capsaicin (EC(50) = 19 μM) stimulated low rates of secretion that were partially inhibited by tetrodotoxin and by inhibitors for muscarinic, VIP, and SubP receptors, suggesting reflex stimulation of secretion by multiple transmitters. Secretion in response to mucosal capsaicin was inhibited by CFTR(inh)-172, but not by niflumic acid. Serosal SubP (EC(50) = 230 nM) stimulated 10-fold more secretion than mucosal capsaicin, with a V(max) similar to that of carbachol. Secretion rates peaked within 5 min and then declined to a lower sustained rate. SubP-stimulated secretion was inhibited 75% by bumetanide, 53% by removal of HCO(3)(-), and 85% by bumetanide + removal of HCO(3)(-); it was not inhibited by atropine but was inhibited by niflumic acid, clotrimazole, BAPTA-AM, nominally Ca(2+)-free bath solution, and the adenylate cyclase inhibitor MDL-12330A. Ratiometric measurements of fura 2 fluorescence in dissociated gland cells showed that SubP and carbachol increased intracellular Ca(2+) concentration by similar amounts. SubP produced rapid volume loss by serous and mucous cells, expansion of gland lumina, mucus flow, and exocytosis but little or no contraction of myoepithelial cells. These and prior results suggest that SubP stimulates pig gland secretion via CFTR- and Ca(2+)-activated Cl(-) channels.
Files in This Item:
T201103066.pdf Download
DOI
10.1152/ajplung.00372.2010
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93857
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links