Effects of Endothelin-1 on Tracheal Submucosal Gland Secretion and Epithelial Function in the Ferret

Endothelins in Health and Disease: An Overview

“…In most species, ET‐1 stimulates receptors in airways linked to a G‐protein and phospholipase C. In airway smooth muscle, this results in contraction following the generation of inositol 1,4,5‐trisphosphate and diacylglycerol (DAG) 18 –20 and increased levels of cytosolic Ca 2+ released from intracellular stores 21 . In some animal species, DAG, through activation of protein kinase C, may also contribute to ET‐1‐induced contraction of airway smooth muscle 22 …”

“…21 In some animal species, DAG, through activation of protein kinase C, may also contribute to ET-1-induced contraction of airway smooth muscle. 22 Numerous studies of airway smooth muscle have demonstrated that at least a part of the ET-1-induced contraction is dependent on the presence of extracellular Ca 2ϩ , 20,23,24 although this may not hold in human bronchus. 11 In some species, including rat, ET-1-induced airway smooth muscle contraction mediated via ETA and ETB receptors uses intracellular and extracellular sources of Ca 2ϩ , respectively.…”

The Endothelins in the Pulmonary System

“…143,[238][239][240][241][242] ET-1 has been reported to produce concentrationfrom cells obtained from bronchoalveolar lavage (BAL) fluid in canine airways 251 and enhanced the dependent increases in the negativity of the transepithelial potential difference 143,242 and in the shortgeneration of oxygen radicals in BAL cells from rats. 252 ET-1 was also reported to potently and effectively circuit current 238,240,242 of epithelial cell cultures, caused by stimulation of Cl − transport across the epistimulate histamine release from guinea-pig pulmonary but not peritoneal mast cells.…”

“…142 Preliminary airway smooth muscle are well established, some evidence suggests that indirect mechanisms involving studies suggest that diacylglycerol, through activation of protein kinase C, might also contribute to ET-1-the release of secondary mediators also operate. For example, in some animal species, inhibitors of cycloinduced contraction of airway smooth muscle in rat 143 and rabbit 144 airways, but not in human, 145 guineaoxygenase have been reported to inhibit, [126][127][128] to potentiate 114,117,129,130 or to have no effect 114,131 on conpig 117 or bovine airways. 127 Although not tested in airway smooth muscle, the slow and sustained nature tractions induced by ET-1.…”